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Background: To date, evidence regarding the effectiveness and safety of individualized controlled ovarian stimulation (COS) compared with standard dose COS has been inadequate., Objectives: To evaluate the updated evidence from published randomized controlled trials (RCTs) about the efficacy and safety of individualized COS with different ovarian reserve test biomarkers or clinical experience versus standard dose COS., Search Strategy: Terms and descriptors related to COS, individualized or standard, and RCT were combined to search, and only English language studies were included. Conference abstracts and comments were excluded., Selection Criteria: RCTs with comparison between different individualized COS strategies and standard starting dose strategy were included., Data Collection and Analysis: Two reviews independently assessed the eligibility of retrieved citations in a predefined standardized manner. Relative risk (RRs) and the weighted mean difference (WMD) with 95% confidence intervals (CIs) were pooled using a random-effects model on R software version 4.2.2., Main Results: Compared with the standard dose COS strategy in pairwise meta-analysis, the individualized COS strategy was associated with a notable lower risk of ovarian hyperstimulation syndrome (OHSS; 174/2384 [7.30%] vs 114/2412 [4.73%], RR 0.66, 95% CI: 0.47-0.93, I 2  = 46%), a significantly lower risk of hyperresponse to stimulation (hyperresponse; 476/2402 [19.82%] vs 331/2437 [13.58%], RR 0.71, 95% CI: 0.57-0.90, I 2  = 61%), and a slightly longer ovarian stimulation days (duration of stimulation; WMD 0.20, 95% CI: 0.01-0.40, I 2  = 66%). Bayesian network meta-analysis also found that biomarker-tailored strategy had a significantly lower risk of OHSS than standard dose strategy (OHSS; RR 0.63, 95% CI: 0.41-0.97, I 2  = 47.5%)., Conclusion: Compared with standard dose COS strategy, individualized COS strategy could significantly reduce the risks of OHSS and hyperresponse to stimulation, but the duration of stimulation was slightly longer., Trial Registration: PROSPERO: CRD42023358439., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Ovarian hyperstimulation syndrome (OHSS) may be a severe complication of controlled ovarian hyperstimulation during assisted reproductive technology. During OHSS, fluid shifts from the intravascular space to the third-space compartments as the result of an increase in capillary permeability. This can cause fluid accumulation in peritoneal as well as thoracic cavities. The patient presented with symptoms of severe OHSS (bilateral hydrothorax and pulmonary effusion), requiring bilateral ultrasound-guided paracentesis and bilateral thoracentesis during her Emergency Room visits and hospitalization. Due to distant effects from the increased capillary permeability, the patient presented fluid in the middle ear, which led to the development of serous otitis media 12 days after egg retrieval. This was resolved 2-3 weeks later after being treated with antihistamines and antibiotics given by her Ear, Nose, and Throat doctor. OHSS risk may be reduced by continuous monitoring of patients undergoing ovulation induction, using an appropriate gonadotropin dosage, and using additional agents known to decrease its risk. If OHSS still occurs, symptomatic treatment and a multidisciplinary team of professionals may be needed to prevent fluid build-up complications. In contrast to many published articles about OHSS and its complications, this is the first case report of a patient presenting serous otitis media as a complication of severe OHSS., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge., Objectives: To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH)., Search Methods: We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase and PsycINFO in Dec 2021. We contacted study authors and experts to identify additional studies., Selection Criteria: We included randomised controlled trials (RCTs) that included progestogens for ovulation inhibition in women undergoing controlled ovarian hyperstimulation (COH)., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane, including the risk of bias (RoB) assessment. The primary review outcomes were live birth rate (LBR) and oocyte pick-up cancellation rate (OPCR). Secondary outcomes were clinical pregnancy rate (CPR), cumulative pregnancy, miscarriage rate (MR), multiple pregnancies, LH surge, total and MII oocytes, days of stimulation, dose of gonadotropins, and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate. The primary analyses were restricted to studies at overall low and some concerns RoB, and sensitivity analysis included all studies. We used the GRADE approach to assess the certainty of evidence., Main Results: We included 14 RCTs (2643 subfertile women undergoing ART, 47 women used oocyte freezing for fertility preservation and 534 oocyte donors). Progestogens versus GnRH antagonists We are very uncertain of the effect of medroxyprogesterone acetate (MPA) 10 mg compared with cetrorelix on the LBR in poor responders (odds ratio (OR) 1.25, 95% confidence interval (CI) 0.73 to 2.13, one RCT, N = 340, very-low-certainty evidence), suggesting that if the chance of live birth following GnRH antagonists is assumed to be 18%, the chance following MPA would be 14% to 32%. There may be little or no difference in OPCR between progestogens and GnRH antagonists, but due to wide Cs (CIs), we are uncertain (OR 0.92, 95%CI 0.42 to 2.01, 3 RCTs, N = 648, I² = 0%, low-certainty evidence), changing the chance of OPCR from 4% with progestogens to 2% to 8%. Given the imprecision found, no conclusions can be retrieved on CPR and MR. Low-quality evidence suggested that using micronised progesterone in normo-responders may increase by 2 to 6 the MII oocytes in comparison to GnRH antagonists. There may be little or no differences in gonadotropin doses. Progestogens versus GnRH agonists Results were uncertain for all outcomes comparing progestogens with GnRH agonists. One progestogen versus another progestogen The analyses comparing one progestogen versus another progestogen for LBR did not meet our criteria for primary analyses. The OPCR was probably lower in the MPA 10 mg in comparison to MPA 4 mg (OR 2.27, 95%CI 0.90 to 5.74, one RCT, N = 300, moderate-certainty evidence), and MPA 4 mg may be lower than micronised progesterone 100 mg, but due to wide CI, we are uncertain of the effect (OR 0.81, 95%CI 0.43 to 1.53, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 5% with MPA 4 mg to 5% to22%, and from 17% with micronised progesterone 100 mg to 8% to 24%. When comparing dydrogesterone 20 mg to MPA, the OPCR is probably lower in the dydrogesterone group in comparison to MPA 10 mg (OR 1.49, 95%CI 0.80 to 2.80, one RCT, N = 520, moderate-certainty evidence), and it may be lower in dydrogesterone group in comparison to MPA 4 mg but due to wide confidence interval, we are uncertain of the effect (OR 1.19, 95%CI 0.61 to 2.34, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 7% with dydrogesterone 20 to 6-17%, and in MPA 4 mg from 12% to 8% to 24%. When comparing dydrogesterone 20 mg to micronised progesterone 100 mg, the OPCR is probably lower in the dydrogesterone group (OR 1.54, 95%CI 0.94 to 2.52, two RCTs, N=550, I² = 0%, moderate-certainty evidence), changing OPCR from 11% with dydrogesterone to 10% to 24%. We are very uncertain of the effect in normo-responders of micronised progesterone 100 mg compared with micronised progesterone 200 mg on the OPCR (OR 0.35, 95%CI 0.09 to 1.37, one RCT, N = 150, very-low-certainty evidence). There is probably little or no difference in CPR and MR between MPA 10 mg and dydrogesterone 20 mg. There may be little or no differences in MII oocytes and gonadotropins doses. No cases of moderate/severe OHSS were reported in most of the groups in any of the comparisons., Authors' Conclusions: Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate the effectiveness of bromocriptine for prevention of ovarian hyperstimulation syndrome (OHSS)., Methods: The retrospective study included women at risk of OHSS who were receiving gonadotropin-releasing hormone antagonist protocols, including 52 women given 2.5 mg bromocriptine by rectal insertion, 52 women given 500 ml intravenous hydroxyethyl starch (HES), and 40 women who received no intervention. Treatments were administered daily for 5 days beginning on the day of oocyte retrieval. Baseline information and data related to OHSS were compared., Results: No significant differences were found among groups in estradiol concentration on the day of trigger or in number of retrieved oocytes. Incidence of mild OHSS was not significantly different among groups, respectively 13.5%, 15.4%, and 17.5% (P > 0.05). The incidence of moderate to severe OHSS was significantly lower in the bromocriptine and HES groups compared with the control group, respectively 7.7%, 5.8%, and 22.5% (P < 0.05). D-dimer levels were significantly lower in the bromocriptine and HES groups compared with the control group on Day 5 after oocyte retrieval (P < 0.05). No differences in liver or renal function were found in the three groups., Conclusion: Bromocriptine was apparently as effective as intravenous HES in patients with high risk of OHSS., (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment.  OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment., Search Methods: We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature., Selection Criteria: We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events., Data Collection and Analysis: Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements  by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence., Main Results: The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage  or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy  or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported., Authors' Conclusions: Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: In vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments conventionally consist of a fresh embryo transfer, possibly followed by one or more cryopreserved embryo transfers in subsequent cycles. An alternative option is to freeze all suitable embryos and transfer cryopreserved embryos in subsequent cycles only, which is known as the 'freeze all' strategy. This is the first update of the Cochrane Review on this comparison., Objectives: To evaluate the effectiveness and safety of the freeze all strategy compared to the conventional IVF/ICSI strategy in women undergoing assisted reproductive technology., Search Methods: We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two registers of ongoing trials from inception until 23 September 2020 for relevant studies, checked references of publications found, and contacted study authors to obtain additional data., Selection Criteria: Two review authors (TZ and MZ) independently selected studies for inclusion, assessed risk of bias, and extracted study data. We included randomised controlled trials comparing a 'freeze all' strategy with a conventional IVF/ICSI strategy including a fresh embryo transfer in women undergoing IVF or ICSI treatment., Data Collection and Analysis: The primary outcomes were cumulative live birth rate and ovarian hyperstimulation syndrome (OHSS). Secondary outcomes included effectiveness outcomes (including ongoing pregnancy rate and clinical pregnancy rate), time to pregnancy and obstetric, perinatal and neonatal outcomes., Main Results: We included 15 studies in the systematic review and eight studies with a total of 4712 women in the meta-analysis. The overall evidence was of moderate to low quality. We graded all the outcomes and downgraded due to serious risk of bias, serious imprecision and serious unexplained heterogeneity. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study during the interim analysis, unit of analysis error, and absence of adequate study termination rules. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below. There is probably little or no difference in cumulative live birth rate between the 'freeze all' strategy and the conventional IVF/ICSI strategy (odds ratio (OR) 1.08, 95% CI 0.95 to 1.22; I 2 = 0%; 8 RCTs, 4712 women; moderate-quality evidence). This suggests that for a cumulative live birth rate of 58% following the conventional strategy, the cumulative live birth rate following the 'freeze all' strategy would be between 57% and 63%. Women might develop less OHSS after the 'freeze all' strategy compared to the conventional IVF/ICSI strategy (OR 0.26, 95% CI 0.17 to 0.39; I 2 = 0%; 6 RCTs, 4478 women; low-quality evidence). These data suggest that for an OHSS rate of 3% following the conventional strategy, the rate following the 'freeze all' strategy would be 1%. There is probably little or no difference between the two strategies in the cumulative ongoing pregnancy rate (OR 0.95, 95% CI 0.75 to 1.19; I 2 = 31%; 4 RCTs, 1245 women; moderate-quality evidence).  We could not analyse time to pregnancy; by design, time to pregnancy is shorter in the conventional strategy than in the 'freeze all' strategy when the cumulative live birth rate is comparable, as embryo transfer is delayed in a 'freeze all' strategy. We are uncertain whether the two strategies differ in cumulative miscarriage rate because the evidence is very low quality (Peto OR 1.06, 95% CI 0.72 to 1.55; I 2 = 55%; 2 RCTs, 986 women; very low-quality evidence) and cumulative multiple-pregnancy rate (Peto OR 0.88, 95% CI 0.61 to 1.25; I 2 = 63%; 2 RCTs, 986 women; very low-quality evidence). The risk of hypertensive disorders of pregnancy (Peto OR 2.15, 95% CI 1.42 to 3.25; I 2 = 29%; 3 RCTs, 3940 women; low-quality evidence), having a large-for-gestational-age baby (Peto OR 1.96, 95% CI 1.51 to 2.55; I 2 = 0%; 3 RCTs, 3940 women; low-quality evidence) and a higher birth weight of the children born (mean difference (MD) 127 g, 95% CI 77.1 to 177.8; I 2 = 0%; 5 RCTs, 1607 singletons; moderate-quality evidence) may be increased following the 'freeze all' strategy. We are uncertain whether the two strategies differ in the risk of having a small-for-gestational-age baby because the evidence is low quality (Peto OR 0.82, 95% CI 0.65 to 1.05; I 2 = 64%; 3 RCTs, 3940 women; low-quality evidence)., Authors' Conclusions: We found moderate-quality evidence showing that one strategy is probably not superior to the other in terms of cumulative live birth rate and ongoing pregnancy rate. The risk of OHSS may be decreased in the 'freeze all' strategy. Based on the results of the included studies, we could not analyse time to pregnancy. It is likely to be shorter using a conventional IVF/ICSI strategy with fresh embryo transfer in the case of similar cumulative live birth rate, as embryo transfer is delayed in a 'freeze all' strategy. The risk of maternal hypertensive disorders of pregnancy, of having a large-for-gestational-age baby and a higher birth weight of the children born may be increased following the 'freeze all' strategy. We are uncertain if 'freeze all' strategy reduces the risk of miscarriage, multiple pregnancy rate or having a small-for-gestational-age baby compared to conventional IVF/ICSI., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates., Objectives: To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS., Search Methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020)., Selection Criteria: Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment., Types of Participants: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment., Primary Outcome Measures: live birth rate, incidence of ovarian hyperstimulation syndrome., Data Collection and Analysis: Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach., Main Results: This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I 2 = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I 2 = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I 2 = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I 2 = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I 2 = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I 2 = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision., Authors' Conclusions: This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate the effect of oral diosmin on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) and explore the value of diosmin in preventing and treating OHSS., Method: A retrospective study of women attending a reproductive center in Guangzhou, China, between September and December 2016. The inclusion criterion was previous cancellation of embryo transfer after oocyte retrieval during IVF owing to a high risk of OHSS. The women were divided into two groups depending on whether they received oral diosmin (1000 mg twice daily for 10 days) after oocyte retrieval (diosmin group) or not (control group). Apart from diosmin, both groups underwent the same treatment. Baseline information and data related to OHSS were compared., Results: Overall, 146 women were included: 74 in the diosmin group and 72 in the control group. The incidence of moderate-to-severe OHSS in the diosmin and control groups was 5/74 (6.2%) and 14/72 (13.4%), respectively (P=0.027). The control group included four cases of paracentesis due to ascites; there were no cases of paracentesis or severe OHSS in the diosmin group., Conclusion: Oral administration of diosmin effectively reduced both the incidence of moderate-to-severe OHSS and the severity of OHSS among high-risk women., (© 2020 International Federation of Gynecology and Obstetrics.)

The objective of this narrative review was to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight women with PCOS the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without adverse effects in the doses recommended, may be suggested. Additional first-line medical alternatives include insulin sensitizers, selective estrogen receptor modulators, and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second-line treatments are ovarian electrocautery and low-dose follicle-stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option as it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Ovarian reserve can be determined by serum anti-Müllerian hormone (AMH) level and/or antral follicle count before controlled ovarian stimulation. The aim of controlled ovarian stimulation is to achieve an appropriate number of mature follicles and avoid complications such as ovarian hyperstimulation syndrome. Measurement of the ovarian reserve is useful for clinicians as it predicts the ovarian response to controlled ovarian stimulation. Further, it assists in giving the patient realistic expectations regarding the treatment. By determining the ovarian reserve, the most appropriate stimulation protocol and gonadotropin dose can be chosen specifically for each woman enabling so-called "individualized treatment" in line with the personalized treatment concept. Many benefits come with using AMH as a biomarker for ovarian reserve; the hormone is considered fairly cycle independent apart from a small decrease in the late follicular phase and there is no inter-observer variance. However, the use of AMH also has limitations; since the implementation of AMH in fertility treatment several AMH assays have been developed. This has made direct comparisons of AMH serum levels complicated. Currently, no international standardized assays exist. AMH is a valid predictor of the ovarian response to controlled ovarian stimulation and to some extent the chance of pregnancy in relation to assisted reproductive technology, but AMH is less optimal in prediction of spontaneous pregnancy and live birth after assisted reproductive technology. Accordingly, AMH can be used to optimize gonadotropin stimulation in fertility treatment, but is not recommended as a screening tool in the general population., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To assess the efficacy of coasting alone, cabergoline alone, or combining both interventions for preventing ovarian hyperstimulation syndrome (OHSS) among high-risk patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles., Methods: The present randomized controlled trial was conducted at the IVF unit of a university hospital in Cairo between October 28, 2013, and July 31, 2015. Patients undergoing IVF/ICSI considered at risk of OHSS were randomly allocated to coasting, cabergoline, or combined coasting and cabergoline. The primary outcome was the rate and degree of symptomatically assessed OHSS. Data were analyzed on a per-protocol basis., Results: There were 100 patients recruited to each group. The occurrence of early OHSS was lowest in the combination group compared with the other groups (P=0.002)., Conclusion: Combining coasting and cabergoline was associated with a lower OHSS rate compared with either therapy alone. CLINICALTRIALS.GOV: NCT01984320., (© 2017 International Federation of Gynecology and Obstetrics.)

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence of moderate to severe OHSS ranges from 0.6% to 5% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intravascular compartment to the third space, resulting in profound intravascular depletion and haemoconcentration., Objectives: To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles., Search Methods: For the update of this review, we searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE (PubMed), CINHAL, PsycINFO, Embase, Google, and clinicaltrials.gov to 6 July 2016., Selection Criteria: We included only randomized controlled trials (RCTs) in which coasting was used to prevent OHSS., Data Collection and Analysis: Two review authors independently selected trials and extracted data. They resolved disagreements by discussion. They contacted study authors to request additional information or missing data. The intervention comparisons were coasting versus no coasting, coasting versus early unilateral follicular aspiration (EUFA), coasting versus gonadotrophin releasing hormone antagonist (antagonist), coasting versus follicle stimulating hormone administration at the time of hCG trigger (FSH co-trigger), and coasting versus cabergoline. We performed statistical analysis in accordance with Cochrane guidelines. Our primary outcomes were moderate or severe OHSS and live birth., Main Results: We included eight RCTs (702 women at high risk of developing OHSS). The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data. Coasting versus no coastingRates of OHSS were lower in the coasting group (OR 0.11, 95% CI 0.05 to 0.24; I² = 0%, two RCTs; 207 women; low-quality evidence), suggesting that if 45% of women developed moderate or severe OHSS without coasting, between 4% and 17% of women would develop it with coasting. There were too few data to determine whether there was a difference between the groups in rates of live birth (OR 0.48, 95% CI 0.14 to 1.62; one RCT; 68 women; very low-quality evidence), clinical pregnancy (OR 0.82, 95% CI 0.46 to 1.44; I² = 0%; two RCTs; 207 women; low-quality evidence), multiple pregnancy (OR 0.31, 95% CI 0.12 to 0.81; one RCT; 139 women; low-quality evidence), or miscarriage (OR 0.85, 95% CI 0.25 to 2.86; I² = 0%; two RCTs; 207 women; very low-quality evidence). Coasting versus EUFAThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 0.98, 95% CI 0.34 to 2.85; I² = 0%; 2 RCTs; 83 women; very low-quality evidence), or clinical pregnancy (OR 0.67, 95% CI 0.25 to 1.79; I² = 0%; 2 RCTs; 83 women; very low-quality evidence); no studies reported live birth, multiple pregnancy, or miscarriage. Coasting versus antagonistOne RCT (190 women) reported this comparison, and no events of OHSS occurred in either arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.74, 95% CI 0.42 to 1.31; one RCT; 190 women; low-quality evidence), or multiple pregnancy rates (OR 1.00, 95% CI 0.43 to 2.32; one RCT; 98 women; very low-quality evidence); the study did not report live birth or miscarriage. Coasting versus FSH co-triggerRates of OHSS were higher in the coasting group (OR 43.74, 95% CI 2.54 to 754.58; one RCT; 102 women; very low-quality evidence), with 15 events in the coasting arm and none in the FSH co-trigger arm. There were too few data to determine whether there was a difference between the groups in clinical pregnancy rates (OR 0.92, 95% CI 0.43 to 2.10; one RCT; 102 women; low-quality evidence). This study did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage, but stated that there was no significant difference between the groups. Coasting versus cabergolineThere were too few data to determine whether there was a difference between the groups in rates of OHSS (OR 1.98, 95% CI 0.09 to 5.68; P = 0.20; I² = 72%; two RCTs; 120 women; very low-quality evidence), with 11 events in the coasting arm and six in the cabergoline arm. The evidence suggested that coasting was associated with lower rates of clinical pregnancy (OR 0.38, 95% CI 0.16 to 0.88; P = 0.02; I² =0%; two RCTs; 120 women; very low-quality evidence), but there were only 33 events altogether. These studies did not report data suitable for analysis on live birth, multiple pregnancy, or miscarriage., Authors' Conclusions: There was low-quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low-quality evidence from a single small study to suggest that using FSH co-trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes.

Background: In general, in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) implies a single fresh and one or more frozen-thawed embryo transfers. Alternatively, the 'freeze-all' strategy implies transfer of frozen-thawed embryos only, with no fresh embryo transfers. In practice, both strategies can vary technically including differences in freezing techniques and timing of transfer of cryopreservation, that is vitrification versus slow freezing, freezing of two pro-nucleate (2pn) versus cleavage-stage embryos versus blastocysts, and transfer of cleavage-stage embryos versus blastocysts.In the freeze-all strategy, embryo transfers are disengaged from ovarian stimulation in the initial treatment cycle. This could avoid a negative effect of ovarian hyperstimulation on the endometrium and thereby improve embryo implantation. It could also reduce the risk of ovarian hyperstimulation syndrome (OHSS) in the ovarian stimulation cycle by avoiding a pregnancy.We compared the benefits and risks of the two treatment strategies., Objectives: To evaluate the effectiveness and safety of the freeze-all strategy compared to the conventional IVF/ICSI strategy in women undergoing assisted reproductive technology., Search Methods: We searched the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Studies (CRSO), MEDLINE, Embase, PsycINFO, CINAHL, and two registers of ongoing trials in November 2016 together with reference checking and contact with study authors and experts in the field to identify additional studies., Selection Criteria: We included randomised clinical trials comparing a freeze-all strategy with a conventional IVF/ICSI strategy which includes fresh transfer of embryos in women undergoing IVF or ICSI treatment., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were cumulative live birth and OHSS. Secondary outcomes included other adverse effects (miscarriage rate)., Main Results: We included four randomised clinical trials analysing a total of 1892 women comparing a freeze-all strategy with a conventional IVF/ICSI strategy. The evidence was of moderate to low quality due to serious risk of bias and (for some outcomes) serious imprecision. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study, unit of analysis error, and absence of adequate study termination rules.There was no clear evidence of a difference in cumulative live birth rate between the freeze-all strategy and the conventional IVF/ICSI strategy (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.91 to 1.31; 4 trials; 1892 women; I 2 = 0%; moderate-quality evidence). This suggests that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 56% and 65%.The prevalence of OHSS was lower after the freeze-all strategy compared to the conventional IVF/ICSI strategy (OR 0.24, 95% CI 0.15 to 0.38; 2 trials; 1633 women; I 2 = 0%; low-quality evidence). This suggests that if the OHSS rate is 7% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 1% and 3%.The freeze-all strategy was associated with fewer miscarriages (OR 0.67, 95% CI 0.52 to 0.86; 4 trials; 1892 women; I 2 = 0%; low-quality evidence) and a higher rate of pregnancy complications (OR 1.44, 95% CI 1.08 to 1.92; 2 trials; 1633 women; low-quality evidence). There was no difference in multiple pregnancies per woman after the first transfer (OR 1.11, 95% CI 0.85 to 1.44; 2 trials; 1630 women; low-quality evidence), and no data were reported for time to pregnancy., Authors' Conclusions: We found moderate-quality evidence showing that one strategy is not superior to the other in terms of cumulative live birth rates. Time to pregnancy was not reported, but it can be assumed to be shorter using a conventional IVF/ICSI strategy in the case of similar cumulative live birth rates, as embryo transfer is delayed in a freeze-all strategy. Low-quality evidence suggests that not performing a fresh transfer lowers the OHSS risk for women at risk of OHSS.

Background: Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33% in its mild form and 3% to 8% in its moderate or severe form. These numbers might even be higher for high-risk women such as those with polycystic ovaries or a high oocyte yield from ovum pickup., Objectives: The objective of this overview is to identify and summarise all evidence from Cochrane systematic reviews on interventions for prevention or treatment of moderate, severe and overall OHSS in couples with subfertility who are undergoing ART cycles., Methods: Published Cochrane systematic reviews reporting on moderate, severe or overall OHSS as an outcome in ART cycles were eligible for inclusion in this overview. We also identified Cochrane submitted protocols and title registrations for future inclusion in the overview. The evidence is current to 12 December 2016. We identified reviews, protocols and titles by searching the Cochrane Gynaecology and Fertility Group Database of Systematic Reviews and Archie (the Cochrane information management system) in July 2016 on the effectiveness of interventions for outcomes of moderate, severe and overall OHSS. We undertook in duplicate selection of systematic reviews, data extraction and quality assessment. We used the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the quality of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables., Main Results: We included a total of 27 reviews in this overview. The reviews were generally of high quality according to AMSTAR ratings, and included studies provided evidence that ranged from very low to high in quality. Ten reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Metformin treatment before and during an ART cycle for women with PCOS (moderate-quality evidence).• Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence).• GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence).• Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence).• Intravenous fluids (plasma expanders) around the time of hCG administration or oocyte pickup in ART cycles (very low-quality evidence).• Progesterone for luteal phase support in ART cycles (low-quality evidence).• Coasting (withholding gonadotrophins) - a promising intervention that needs to be researched further for reduction of OHSS.On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of embryo cryopreservation., Authors' Conclusions: Currently, 27 reviews in the Cochrane Library were conducted to report on or to try to report on OHSS in ART cycles. We identified four review protocols but no new registered titles that can potentially be included in this overview in the future. This overview provides the most up-to-date evidence on prevention of OHSS in ART cycles from all currently published Cochrane reviews on ART. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise other outcomes such as pregnancy or live birth rate. Review results, however, are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.

Background: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. The dopamine agonist cabergoline was introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. As cabergoline seemed to be effective in preventing OHSS, other types of dopamine agonists, such as quinagolide and bromocriptine, have since been studied in ART to prevent OHSS., Objectives: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in high-risk women undergoing ART treatment., Search Methods: We searched several databases from inception to August 2016 (Cochrane Gynaecology and Fertility Specialised Register of trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Clinicaltrials.gov and the World Health Organization International Trials Registry Platform (ICTRP)) for randomised controlled trials (RCTs) assessing the effect of dopamine agonist in preventing OHSS. We handsearched the reference lists of relevant studies., Selection Criteria: We considered RCTs which compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in high-risk women for inclusion. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment., Data Collection and Analysis: Two authors independently screened titles, abstracts and full texts of publications, selected studies, extracted data and assessed risk of bias. We resolved any disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method. In addition, we graded the overall quality of the evidence using GRADE criteria., Main Results: The search identified 14 new RCTs since the last published version of this review, resulting in 16 included RCTs involving 2091 high-risk women for this updated review. They evaluated three types of dopamine agonists: cabergoline, quinagolide and bromocriptine.When compared with placebo or no intervention, dopamine agonists seemed effective in the prevention of moderate or severe OHSS (OR 0.27, 95% CI 0.19 to 0.39; 1022 participants; 8 studies; I 2 = 0%; moderate quality evidence). This suggests that if 29% of women undergoing ART experience moderate or severe OHSS, the use of dopamine agonists will lower this to 7% to 14% of women. There was no evidence of a difference in live birth rate, clinical pregnancy rate, multiple pregnancy rate or miscarriage rate (very low to moderate quality evidence). However, taking dopamine agonists (especially quinagolide) may increase the incidence of adverse events such as gastrointestinal adverse effects (OR 4.54, 95% CI 1.49 to 13.84; 264 participants; 2 studies; I 2 = 49%, very low quality evidence).When we compared dopamine agonist plus co-intervention with co-intervention, there was no evidence of a difference in the outcomes of moderate or severe OHSS, live birth rate, clinical pregnancy rate, miscarriage rate or adverse events. The co-interventions were hydroxyethyl starch (two RCTs) and albumin (one RCT).Cabergoline was associated with a lower risk of moderate or severe OHSS compared with human albumin (OR 0.21, 95% CI 0.12 to 0.38; 296 participants; 3 studies; I 2 = 72%). However, there was no evidence of a difference between cabergoline and hydroxyethyl starch, coasting (withholding any more ovarian stimulation for a few days) or prednisolone. There was an increased clinical pregnancy rate in the cabergoline group when cabergoline was compared with coasting (OR 2.65, 95% CI 1.13 to 6.21; 120 participants; 2 studies; I 2 = 0%). In other respects, there was no evidence of a difference in clinical pregnancy rate, multiple pregnancy rate or miscarriage rate between cabergoline and other active interventions.The quality of the evidence between dopamine agonist and placebo or no intervention ranged from very low to moderate, mainly due to poor reporting of study methods (mostly a lack of details on randomisation or blinding) and serious imprecision for some comparisons., Authors' Conclusions: Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence). If a fresh embryo transfer is performed, the use of dopamine agonists does not affect the pregnancy outcome (live birth rate, clinical pregnancy rate and miscarriage rate) (very low to moderate quality evidence). However, dopamine agonists might increase the risk of adverse events, such as gastrointestinal symptoms. Further research should focus on dose-finding, comparisons with other effective treatments and consideration of combination treatments. Therefore, large, well-designed and well-executed RCTs that involve more clinical endpoints (e.g., live birth rate) are necessary to further evaluate the role of dopamine agonists in OHSS prevention.

Background: Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially fatal complication of ovarian stimulation which affects 1% to 14% of all in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. A number of clinical studies with conflicting results have reported on the use of plasma expanders such as albumin, hydroxyethyl starch (HES), mannitol, polygeline and dextran as a possible intervention for the prevention of OHSS. Women with very high estradiol levels, high numbers of follicles or oocytes retrieved, and women with polycystic ovary syndrome (PCOS), are at particularly high risk of developing OHSS. Plasma expanders are not commonly used nowadays in ovarian hyperstimulation. This is mainly because clinical evidence on their effectiveness remains sparse, because of the low incidence of moderate and severe ovarian hyperstimulation syndrome (OHSS) and the simultaneous introduction of mild stimulation approaches, gonadotropin-releasing hormone (GnRH) antagonist protocols and the freeze-all strategy for the prevention of OHSS., Objectives: To review the effectiveness and safety of administration of volume expanders for the prevention of moderate and severe ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing IVF or ICSI treatment cycles., Search Methods: We searched databases including the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and trial registers to September 2015; no date restrictions were used as new comparators were included in this search. The references of relevant publications were also searched. We attempted to contact authors to provide or clarify data that were unclear from trial or abstract reports., Selection Criteria: We included randomised controlled trials (RCTs) comparing volume expanders versus placebo or no treatment for the prevention of OHSS in high-risk women undergoing ovarian hyperstimulation as part of any assisted reproductive technique., Data Collection and Analysis: Two review authors independently selected the studies, assessed risk of bias and extracted relevant data. The primary review outcome was moderate or severe OHSS. Other outcomes were live birth, pregnancy and adverse events. We combined data to calculate pooled Peto odds ratios (ORs) and 95% confidence intervals (CIs) for each intervention. Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for each comparison, using GRADE methods., Main Results: We included nine RCTs (1867 women) comparing human albumin (seven RCTs) or HES (two RCTs) or mannitol (one RCT) versus placebo or no treatment for prevention of OHSS. The evidence was very low to moderate quality for all comparisons. The main limitations were imprecision, poor reporting of study methods, and failure to blind outcome assessment.There was evidence of a beneficial effect of intravenous albumin on OHSS, though heterogeneity was substantial (Peto OR 0.67 95% CI 0.47 to 0.95, seven studies, 1452 high risk women; I² = 69%, very low quality evidence) . This suggests that if the rate of moderate or severe OHSS with no treatment is 12%, it will be about 9% (6% to12%) with the use of intravenous albumin. However, there was evidence of a detrimental effect on pregnancy rates (Peto OR 0.72 95% CI 0.55 to 0.94, I² = 42%, seven studies 1069 high risk women, moderate quality evidence). This suggests that if the chance of pregnancy is 40% without treatment, it will be about 32% (27% to 38%) with the use of albumin.There was evidence of a beneficial effect of HES on OHSS (Peto OR 0.27 95% CI 0.12 to 0.59, I² = 0%, two studies, 272 women, very low quality evidence). This suggests that if the rate of moderate or severe OHSS with no treatment is 16%, it will be about 5% (2% to 10%) with the use of HES. There was no evidence of an effect on pregnancy rates (Peto OR 1.20 95% CI 0.49 to 2.93, one study, 168 women, very low quality evidence).There was evidence of a beneficial effect of mannitol on OHSS (Peto OR 0.38, 95% CI 0.22 to 0.64, one study, 226 women with PCOS, low quality evidence). This means that if the risk of moderate or severe OHSS with no treatment is 52%, it will be about 29% (19% to 41%) with mannitol. There was no evidence of an effect on pregnancy rates (Peto OR 0.85 95% CI 0.47 to 1.55; one study, 226 women, low quality evidence).Live birth rates were not reported in any of the studies. Adverse events appeared to be uncommon, but were too poorly reported to reach any firm conclusions., Authors' Conclusions: Evidence suggests that the plasma expanders assessed in this review (human albumin, HES and mannitol) reduce rates of moderate and severe OHSS in women at high risk. Adverse events appear to be uncommon, but were too poorly reported to reach any firm conclusions, and there were no data on live birth. However, there was evidence that human albumin reduces pregnancy rates. While there was no evidence that HES, or mannitol had any influence on pregnancy rates, the evidence of effectiveness was based on very few trials which need to be confirmed in additional, larger randomised controlled trials (RCTs) before they should be considered for routine use in clinical practice.

Background: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotrophin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimens have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006 and 2011., Objectives: To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists compared with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycles., Search Methods: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched from inception to May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to 28 April 2015), Ovid MEDLINE (1966 to 28 April 2015), EMBASE (1980 to 28 April 2015), PsycINFO (1806 to 28 April 2015), CINAHL (to 28 April 2015) and trial registers to 28 April 2015, and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). We contacted the authors of eligible studies for missing or unpublished data. The evidence is current to 28 April 2015., Selection Criteria: Two review authors independently screened the relevant citations for randomised controlled trials (RCTs) comparing different GnRH agonist versus GnRH antagonist protocols in women undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI)., Data Collection and Analysis: Two review authors independently assessed trial eligibility and risk of bias, and extracted the data. The primary review outcomes were live birth and ovarian hyperstimulation syndrome (OHSS). Other adverse effects (miscarriage and cycle cancellation) were secondary outcomes. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic. We assessed the overall quality of the evidence for each comparison using GRADE methods., Main Results: We included 73 RCTs, with 12,212 participants, comparing GnRH antagonist to long-course GnRH agonist protocols. The quality of the evidence was moderate: limitations were poor reporting of study methods.Live birthThere was no conclusive evidence of a difference in live birth rate between GnRH antagonist and long course GnRH agonist (OR 1.02, 95% CI 0.85 to 1.23; 12 RCTs, n = 2303, I(2)= 27%, moderate quality evidence). The evidence suggested that if the chance of live birth following GnRH agonist is assumed to be 29%, the chance following GnRH antagonist would be between 25% and 33%.OHSSGnRH antagonist was associated with lower incidence of any grade of OHSS than GnRH agonist (OR 0.61, 95% C 0.51 to 0.72; 36 RCTs, n = 7944, I(2) = 31%, moderate quality evidence). The evidence suggested that if the risk of OHSS following GnRH agonist is assumed to be 11%, the risk following GnRH antagonist would be between 6% and 9%.Other adverse effectsThere was no evidence of a difference in miscarriage rate per woman randomised between GnRH antagonist group and GnRH agonist group (OR 1.04, 95% CI 0.82 to 1.30; 33 RCTs, n = 7022, I(2) = 0%, moderate quality evidence).With respect to cycle cancellation, GnRH antagonist was associated with a lower incidence of cycle cancellation due to high risk of OHSS (OR 0.47, 95% CI 0.32 to 0.69; 19 RCTs, n = 4256, I(2) = 0%). However cycle cancellation due to poor ovarian response was higher in women who received GnRH antagonist than those who were treated with GnRH agonist (OR 1.32, 95% CI 1.06 to 1.65; 25 RCTs, n = 5230, I(2) = 68%; moderate quality evidence)., Authors' Conclusions: There is moderate quality evidence that the use of GnRH antagonist compared with long-course GnRH agonist protocols is associated with a substantial reduction in OHSS without reducing the likelihood of achieving live birth.

Background: As many as one in six couples will encounter problems with fertility, defined as failure to achieve a clinical pregnancy after regular intercourse for 12 months. Increasingly, couples are turning to assisted reproductive technology (ART) for help with conceiving and ultimately giving birth to a healthy live baby of their own. Fertility treatments are complex, and each ART cycle consists of several steps. If one of the steps is incorrectly applied, the stakes are high as conception may not occur. With this in mind, it is important that each step of the ART cycle is supported by good evidence from well-designed studies., Objectives: To summarise the evidence from Cochrane systematic reviews on procedures and treatment options available to couples with subfertility undergoing assisted reproductive technology (ART)., Methods: Published Cochrane systematic reviews of couples undergoing ART (in vitro fertilisation or intracytoplasmic sperm injection) were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation, for future inclusion.The outcomes of the overview were live birth (primary outcome), clinical pregnancy, multiple pregnancy, miscarriage and ovarian hyperstimulation syndrome (secondary outcomes). Studies of intrauterine insemination and ovulation induction were excluded.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed by using the AMSTAR tool. Reviews were organised by their relevance to specific stages in the ART cycle. Their findings were summarised in the text and data for each outcome were reported in 'Additional tables'., Main Results: Fifty-nine systematic reviews published in The Cochrane Library up to July 2015 were included. All were high quality. Thirty-two reviews identified interventions that were effective (n = 19) or promising (n = 13), 14 reviews identified interventions that were either ineffective (n = 2) or possibly ineffective (n = 12), and 13 reviews were unable to draw conclusions due to lack of evidence.An additional 11 protocols and five titles were identified for future inclusion in this overview., Authors' Conclusions: This overview provides the most up to date evidence on ART cycles from systematic reviews of randomised controlled trials. Fertility treatments are costly and the stakes are high. Using the best available evidence to optimise outcomes is best practice. The evidence from this overview could be used to develop clinical practice guidelines and protocols for use in daily clinical practice, in order to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation and ovarian hyperstimulation syndrome.

Background: As many as one in six couples will encounter problems with fertility, defined as failure to achieve a clinical pregnancy after regular intercourse for 12 months. Increasingly, couples are turning to assisted reproductive technology (ART) for help with conceiving and ultimately giving birth to a healthy live baby of their own. Fertility treatments are complex, and each ART cycle consists of several steps. If one of the steps is incorrectly applied, the stakes are high as conception may not occur. With this in mind, it is important that each step of the ART cycle is supported by good evidence from well-designed studies., Objectives: To summarise the evidence from Cochrane systematic reviews on procedures and treatment options available to couples with subfertility undergoing assisted reproductive technology (ART)., Methods: Published Cochrane systematic reviews of couples undergoing ART (in vitro fertilisation or intracytoplasmic sperm injection) were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation, for future inclusion.The outcomes of the overview were live birth (primary outcome), clinical pregnancy, multiple pregnancy, miscarriage and ovarian hyperstimulation syndrome (secondary outcomes). Studies of intrauterine insemination and ovulation induction were excluded.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed by using the AMSTAR tool. Reviews were organised by their relevance to specific stages in the ART cycle. Their findings were summarised in the text and data for each outcome were reported in 'Additional tables'., Main Results: Fifty-eight systematic reviews published in The Cochrane Library were included. All were high quality. Thirty-two reviews identified interventions that were effective (n = 19) or promising (n = 13), 14 reviews identified interventions that were either ineffective (n = 3) or possibly ineffective (n=11), and 12 reviews were unable to draw conclusions due to lack of evidence.An additional 11 protocols and one title were identified for future inclusion in this overview., Authors' Conclusions: This overview provides the most up to date evidence on ART cycles from systematic reviews of randomised controlled trials. Fertility treatments are costly and the stakes are high. Using the best available evidence to optimise outcomes is best practice. The evidence from this overview could be used to develop clinical practice guidelines and protocols for use in daily clinical practice, in order to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation and ovarian hyperstimulation syndrome.

Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-releasing hormone antagonist protocol should be the protocol of choice for the PCOS patient undergoing ovarian stimulation with gonadotropins for in vitro fertilization. If an excessive ovarian response is encountered, the clinician will always have two options: either to trigger final oocyte maturation with a bolus of GnRHa and supplement the luteal phase with a small bolus of human chorionic gonadotropin in addition to the standard luteal phase support and transfer in the fresh cycle or, alternatively, to trigger with GnRHa and perform a total freeze, resulting in a complete elimination of OHSS and high ongoing pregnancy rates in the subsequent frozen-thawed transfer cycles., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Ovarian hyperstimulation syndrome (OHSS) is a complication resulting from administration of human chorionic gonadotrophin (hCG) in assisted reproduction technology (ART) treatment. Most case are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Recently, the dopamine agonist cabergoline has been introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS who are undergoing ART treatment., Objectives: To assess the effectiveness and safety of cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing ART treatment., Search Methods: Major medical databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and PsycINFO) were systematically searched for randomised controlled trials (RCTs) assessing the effect of cabergoline in preventing OHSS. Databases were searched up to September 2011. Registers of clinical trials, abstracts of scientific meetings and reference lists of included studies were searched. No language restrictions were applied., Selection Criteria: RCTs which compared cabergoline with placebo, no treatment or another intervention for preventing OHSS in high-risk women were considered for inclusion. Primary outcome measures included incidence of moderate or severe OHSS and live birth rate. Secondary endpoints were clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and any other adverse effects of the treatment., Data Collection and Analysis: Two authors independently screened titles, abstracts and the full text of publications; extracted data; and assessed risk of bias. Any disagreements were resolved by consensus. Pooled results were reported as odds ratio (OR) and 95% confidence interval (95% CI) by the Mantel-Haenszel method., Main Results: Only two trials involving 230 women met the inclusion criteria. Both studies had a moderate risk of bias. Oral cabergoline, 0.5 mg daily, was given as an intervention and compared with a matched placebo. A statistically significant reduction in OHSS was observed in the cabergoline treated group (OR 0.40, 95% CI 0.20 to 0.77; 2 RCTs, 230 women) with a number needed to treat (NTT) of 7. There was a statistically significant difference in the incidence of moderate OHSS, favouring cabergoline (OR 0.38, 95% CI 0.19 to 0.78; 2 RCTs, 230 women) but not in severe OHSS (OR 0.77, 95% CI 0.24 to 2.45; 2 RCTs, 230 women). There was no significant difference in the clinical pregnancy rate (OR 0.94, 95% CI 0.56 to 1.59; 2 RCTs, 230 women), miscarriage rate (OR 0.31, 95% CI 0.03 to 3.07; 1 RCT, 163 women) or any other adverse effects of the treatment (OR 2.07, 95% CI 0.56 to 7.70; 1 RCT, 67 women). However, no data on multiple pregnancy rate or live birth rate were reported in either trial., Authors' Conclusions: Cabergoline appears to reduce the risk of OHSS in high-risk women, especially for moderate OHSS. The use of cabergoline does not affect the pregnancy outcome (clinical pregnancy rate, miscarriage rate), nor is there an increased risk of adverse events. Further research should consider the risk of administering cabergoline and the comparison between cabergoline and established treatments (such as intravenous albumin and coasting). Large, well-designed and well-executed RCTs that involve more clinical endpoints are necessary to further evaluate the role of cabergoline in OHSS prevention.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and haemoconcentration., Objectives: To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles., Search Strategy: For the update of this review we searched the Cochrane Menstrual Disorders and Subfertility Review Group Trials Register (July 2010), CENTRAL (inception to July 2010), MEDLINE (PubMed) (inception to July 2010), and EMBASE (inception to July 2010) for randomised controlled trials (RCTs) in which coasting was used to prevent OHSS., Selection Criteria: Only randomised controlled trials (RCTs) in which coasting was used to prevent OHSS were included., Data Collection and Analysis: Two review authors independently selected trials and extracted data. Disagreements were resolved by discussion. Study authors were contacted to request additional information or missing data. The intervention comparisons were coasting versus early unilateral follicular aspiration (EUFA), no coasting or other interventions. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines., Main Results: This updated review identified 16 studies of which four met the inclusion criteria. There was no evidence of a difference in the incidence of moderate and severe OHSS (odds ratio (OR) 0.53, 95% CI 0.23 to 1.23), live birth (OR 0.48, 95% CI 0.14 to 1.62; P = 0.24) or in the clinical pregnancy rate (OR 0.69, 95% CI 0.44 to 1.08) between the groups. Significantly fewer oocytes were retrieved in coasting groups compared with GnRHa (OR -2.44, 95% CI -4.30 to -0.58; P = 0.01) or no coasting (OR -3.92, 95% CI -4.47 to -3.37; P < 0.0001). Data for coasting versus EUFA were not pooled for number of oocytes retrieved due to heterogeneity (I(2) = 87%)., Authors' Conclusions: There was no evidence to suggest a benefit of using coasting to prevent OHSS compared with no coasting or other interventions.

Background: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-estrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists directly and rapidly inhibit gonadotropin release within several hours through competitive binding to pituitary GnRH receptors. This property allows their use at any time during the follicular phase. Several different regimes have been described including multiple-dose fixed (0.25 mg daily from day six to seven of stimulation), multiple-dose flexible (0.25 mg daily when leading follicle is 14 to 15 mm), and single-dose (single administration of 3 mg on day 7 to 8 of stimulation) protocols, with or without the addition of an oral contraceptive pill. Further, women receiving antagonists have been shown to have a lower incidence of ovarian hyperstimulation syndrome (OHSS). Assuming comparable clinical outcomes for the antagonist and agonist protocols, these benefits would justify a change from the standard long agonist protocol to antagonist regimens. This is an update of a Cochrane review first published in 2001, and previously updated in 2006., Objectives: To evaluate the effectiveness and safety of gonadotrophin-releasing hormone (GnRH) antagonists with the standard long protocol of GnRH agonists for controlled ovarian hyperstimulation in assisted conception cycle, Search Strategy: We performed electronic searches of major databases, for example Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL, MEDLINE, EMBASE (from 1987 to April 2010); and handsearched bibliographies of relevant publications and reviews, and abstracts of major scientific meetings, for example the European Society of Human Reproduction and Embryology (ESHRE) and American Society for Reproductive Medicine (ASRM). A date limited search of Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL from April 2010 to April 2011 was run. Eighteen studies have been entered into the Classification pending references section of this update. These studies will be appraised for inclusion or exclusion in the next update of this review, due April 2012., Selection Criteria: Two review authors independently screened the relevant citations for randomised controlled trials (RCTs) comparing different agonist versus antagonist protocols in women undergoing IVF or ICSI., Data Collection and Analysis: Two review authors independently assessed trial risk of bias and extracted data. If relevant data were missing or unclear, the authors were contacted for clarification., Main Results: Forty-five RCTs (n = 7511) comparing the antagonist to the long agonist protocols fulfilled the inclusion criteria. There was no evidence of a statistically significant difference in rates of live-births (9 RCTs; odds ratio (OR) 0.86, 95% CI 0.69 to 1.08) or ongoing pregnancy (28 RCTs; OR 0.87, 95% CI 0.77 to 1.00). There was a statistically significant lower incidence of OHSS in the GnRH antagonist group (29 RCTs; OR 0.43, 95% CI 0.33 to 0.57)., Authors' Conclusions: The use of antagonist compared with long GnRH agonist protocols was associated with a large reduction in OHSS and there was no evidence of a difference in live-birth rates.

Background: Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially fatal complication of ovarian stimulation, which affects 1% to 14% of all in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. A number of clinical studies with conflicting results have reported on the use of intravenous fluids such as albumin, hydroxyethyl starch, Haemaccel® and dextran as a possible way for preventing the severe form of OHSS., Objectives: To review the effectiveness and safety of administration of intravenous fluids such as albumin, hydroxyethyl starch, Haemaccel® and dextran in the prevention of severe ovarian hyperstimulation syndrome (OHSS) in IVF or ICSI treatment cycles., Search Strategy: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, to third quarter 2010), MEDLINE (1950 to November 2010), EMBASE (1980 to November 2010) and The National Research Register (to November 2010). The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. The authors were contacted to provide or clarify data that were unclear from the trial reports., Selection Criteria: Randomised controlled trials (RCTs) which compared the effects of intravenous fluids with placebo or no treatment for the prevention of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles., Data Collection and Analysis: Two review authors independently scanned the abstracts, identified relevant papers, assessed inclusion of trials and trial quality and extracted relevant data. Validity was assessed in terms of method of randomisation, allocation concealment and outcomes. Where possible, data were pooled for analysis. A separate analysis of studies was performed for human albumin and hydroxyethyl starch versus placebo or no treatment. Other potential intravenous fluids have been identified, such as Haemaccel and dextran, however no randomised controlled studies on their applicability could be found., Main Results: Nine RCTs involving 1660 (human albumin vs placebo) and 487 (HES vs placebo) randomised women, have been included in this review. There was a borderline statistically significant decrease in the incidence of severe OHSS with administration of human albumin (8 RCTs, OR 0.67, 95% CI 0.45 to 0.99).There was a statistically significant decrease in severe OHSS incidence with administration of hydroxyethyl starch (3 RCTs, OR 0.12, 95% CI 0.04 to 0.40). There was no evidence of statistical difference in the pregnancy rate between both groups of treatment., Authors' Conclusions: There is limited evidence of benefit from intra-venous albumin administration at the time of oocyte retrieval in the prevention or reduction of the incidence of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles. Hydroxyethyl starch markedly decreases the incidence of severe OHSS.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors contributing to OHSS have not been completely explained. The release of vasoactive substances secreted by the ovaries under human chorionic gonadotrophin (hCG) stimulation may play a key role in triggering this syndrome. This condition is characterised by a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and haemoconcentration., Objectives: To assess the effect of withholding gonadotrophins (coasting) on the prevention of ovarian hyperstimulation syndrome in assisted reproduction cycles., Search Strategy: For the update of this review we searched the Cochrane Menstrual Disorders and Subfertility Review Group Trials Register (July 2010), CENTRAL (inception to July 2010), MEDLINE (PubMed) (inception to July 2010), and EMBASE (inception to July 2010) for randomised controlled trials (RCTs) in which coasting was used to prevent OHSS., Selection Criteria: Only randomised controlled trials (RCTs) in which coasting was used to prevent OHSS were included., Data Collection and Analysis: Two review authors independently selected trials and extracted data. Disagreements were resolved by discussion. Study authors were contacted to request additional information or missing data. The intervention comparisons were coasting versus early unilateral follicular aspiration (EUFA), no coasting or other interventions. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines., Main Results: This updated review identified 16 studies of which four met the inclusion criteria. There was no evidence of a difference in the incidence of moderate and severe OHSS (odds ratio (OR) 0.53, 95% CI 0.23 to 1.23), live birth (OR 0.48, 95% CI 0.14 to 1.62; P = 0.24) or in the clinical pregnancy rate (OR 0.69, 95% CI 0.44 to 1.08) between the groups. Significantly fewer oocytes were retrieved in coasting groups compared with GnRHa (OR -2.44, 95% CI -4.30 to -0.58; P = 0.01) or no coasting (OR -3.92, 95% CI -4.47 to -3.37; P < 0.0001). Data for coasting versus EUFA were not pooled for number of oocytes retrieved due to heterogeneity (I(2) = 87%)., Authors' Conclusions: There was no evidence to suggest a benefit of using coasting to prevent OHSS compared with no coasting or other interventions.

Background: Endometriomata are cysts of endometriosis in the ovaries. As artificial reproductive technology (ART) cycles involve oocyte pickup from the ovaries, endometriomata may interfere with the outcome of ART., Objectives: To determine the effectiveness and safety of surgery, medical treatment, combination therapy or no treatment for improving reproductive outcomes among women with endometriomata, prior to undergoing ART cycles., Search Strategy: The review authors searched: Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, CENTRAL (The Cochrane Library), EMBASE, MEDLINE, PubMed, PsycINFO, CINAHL, DARE, trial registers for ongoing and registered trials, citation indexes, conference abstracts on the ISI Web of Knowledge, Clinical Study Results, OpenSIGLE (July 2010) and handsearched Fertility and Sterility (2008 to 2010)., Selection Criteria: Randomised controlled trials of any medical, surgical or combination therapy or expectant management for endometriomata prior to ART., Data Collection and Analysis: The trials were independently identified and assessed for risk of bias by two authors. The authors of the trials that were potentially eligible for inclusion were contacted for additional information. Outcomes were expressed as Peto odds ratios and mean differences (MD)., Main Results: Eleven trials were identified of which seven were excluded and four with 312 participants were included.No trial reported live birth outcomes. One trial compared gonadotropin-releasing hormone (GnRH) agonist with GnRH antagonist. There was no evidence of a difference for clinical pregnancy rate (CPR), however the number of mature oocytes retrieved (NMOR) was greater with GnRH agonists (MD -1.60, 95% CI -2.44 to -0.76) and the ovarian response was increased (estradiol (E2) levels on day of human chorionic gonadotropin (hCG) injection) (MD -456.30, 95% CI -896.06 to -16.54).Surgery (aspiration or cystectomy) versus expectant management (EM) showed no evidence of a benefit for clinical pregnancy with either technique. Aspiration was associated with greater NMOR (MD 0.50, 95% CI 0.02 to 0.98) and increased ovarian response (E2 levels on day of hCG injection) (MD 685.3, 95% CI 464.50 to 906.10) compared to EM.Cystectomy was associated with a decreased ovarian response to controlled ovarian hyperstimulation (COH) (MD -510.00, 95% CI -676.62 to -343.38); no evidence of an effect on the NMOR compared to EM. Aspiration versus cystectomy showed no evidence of a difference in CPR or the NMOR., Authors' Conclusions: There was no evidence of an effect on reproductive outcomes in any of the four included trials. Further RCTs of management of endometrioma in women undergoing ART are required.

Objective: To compare the efficacy of cabergoline (Cb2) and meloxicam in curbing vascular endothelial growth factor (VEGF) expression and preventing ovarian hyperstimulation syndrome (OHSS)., Design: Randomized controlled, animal study., Setting: Academic facility., Sample: We used a total of 50 immature Wistar female rats randomly to create an experimental OHSS model., Methods: Ten rats each formed the control group and mild OHSS group. The remaining 30 were separated into three equal groups of severe OHSS. Mild and severe OHSS were induced through ovarian stimulation with gonadotropins. One group with severe OHSS was administered a low-dose 100 microg/kg Cb2 therapy; another group with severe OHSS received 600 microg/kg meloxicam. Body weight, vascular permeability (VP), VEGF expression, ovary weight, and diameter were then compared., Main Outcome Measures: The efficacy of Cb2 and meloxicam for preventing OHSS., Results: Comparison of the severe OHSS groups with the controls and mild OHSS group revealed significant increases in VEGF expression, VP, ovary weight, and diameter. The increase in VEGF expression was demonstrated to be dependent on human chorionic gonadotropin doses. However, low-dose Cb2 and meloxicam therapies were shown to be ineffective in decreasing VEGF expression and VP, ovary weight, and ovary diameter in severe OHSS., Conclusions: VEGF elevation played a critical part in OHSS pathogenesis, but the therapies administered failed to curb VEGF expression.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic potentially life threatening condition resulting from an excessive ovarian stimulation. Its reported incidence varies from one percent to ten percent of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and haemoconcentration., Objectives: To evaluate (i) the effectiveness of cryopreservation (embryo freezing) for the prevention of OHSS when compared with human intra-venous albumin infusion (ii) the effectiveness of the elective cryopreservation (embryo freezing ) of all embryos for the prevention of OHSS when compared with fresh embryo transfer., Search Strategy: We searched the Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials up to April 2007. In addition, MEDLINE (PUBMED 1985 to March 2007), EMBASE (1985 to April 2007), CINAHL (1985 to March 2007) and the National Research Register (April 2007) were searched., Selection Criteria: Randomised controlled trials (RCTs) in which either human intra-venous albumin or cryopreservation of all embryos were used as a therapeutic approach to OHSS were included. The women were women of reproductive age who were down regulated by gonadotrophin-releasing hormone-analogue (GnRH-a), undergoing superovulation in in vitro fertilization and or intra-cytoplasmic sperm injection (IVF and or ICSI) cycles., Data Collection and Analysis: Two review authors, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion . Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing to the corresponding authors directly. The interventions compared were cryopreservation (embryo freezing) versus intra-venous human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil and or mild OHSS, clinical pregnancies and or woman. The secondary outcomes were: number of oocytes retrieved, number of oocytes fertilized, number of embryos transferred, number of embryos frozen, multiple pregnancy rate, live birth rate, number of women admitted to the hospital as inpatient or outpatient and time to the next menstrual period (resolution time). Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines., Main Results: No new studies were identified for inclusion in the update therefore the of seventeen studies originally identified in the review published issue 2, 2002. It therefore remains that two studies of which met our inclusion criteria one study was included where cryopreservation (embryo freezing) was compared with intra-venous human albumin administration (Shaker 1996) and one study was included where elective cryopreservation of all embryos was compared with fresh embryo transfer (Ferraretti 1999). When cryopreservation was compared with intra-venous human albumin administration no difference was found in all the outcomes examined between the two groups. When elective cryopreservation of all embryos was compared with fresh embryo transfer no difference was found in all the outcomes examined between the two groups., Authors' Conclusions: This updated of the review (D'Angelo 2002) has showed that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of intra-venous albumin versus cryopreservation.

Background: The aims of this study were to investigate whether a high dose of gonadotrophin-releasing hormone antagonist during the preceding luteal phase yields satisfactory luteolysis and downregulation prior to ovarian hyperstimulation in an in vitro fertilization program., Methods: The treatment protocol was designed as a prospective pilot study in IVF units at two university hospitals. Fifty-one patients with documented poor or normal response to ovarian stimulation underwent 57 treatment cycles. Treatment consisted of 3 mg gonadotrophin-releasing hormone antagonist (cetrorelix) given during the preceding mid-luteal phase as gonadotrophin-releasing hormone-receptor inhibition before ovarian stimulation with follicle-stimulating hormone., Results: All women experienced menstrual bleeding within 2-3 days after the injection of 3 mg cetrorelix. Follicle hormone stimulation could subsequently commence in all cycles. All but three patients developed growing follicles and underwent oocyte retrieval. Seventy-five percent of started cycles reached transfer of one or two good-quality embryos., Conclusions: A single high-dose gonadotrophin-releasing hormone antagonist given during the preceding luteal phase presents a new and feasible protocol to initiate controlled ovarian hyperstimulation in an in vitro fertilization program.

Background: Traditional monitoring of an in vitro fertilization (IVF) treatment cycle includes regular estradiol levels and ultrasound scans in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for estradiol monitoring remains controversial., Methods: We reviewed 538 consecutive cycles of IVF that were carried out in our unit to ascertain whether routine estradiol monitoring was of help in preventing OHSS and could be used to predict treatment outcome. Two hundred and sixty-eight patients had their ovarian response monitored with ultrasound (USS) and estradiol levels on the day of hCG administration. The following 270 had USS monitoring but only had an estradiol level checked if they were deemed to be at high risk of OHSS (> 20 follicles on USS or symptomatic)., Results: Pregnancy rates per treatment cycle and per embryo transfer were similar in the two groups (all p > 0.05). There were two patients in each group requiring admission to hospital for OHSS., Conclusions: Estradiol levels did not correlate with IVF outcome. In summary therefore estradiol levels are a poor predictor of treatment success and done routinely do not reduce the incidence of OHSS. It is only necessary to measure the estradiol level in those patients at risk of OHSS on USS monitoring.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic potentially life threatening condition resulting from an excessive ovarian stimulation. Its reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and hemoconcentration., Objectives: To evaluate (i) the effectiveness of cryopreservation (embryo freezing) for the prevention of OHSS when compared with human intra-venous albumin infusion and (ii) the effectiveness of the elective cryopreservation (embryo freezing ) of all embryos for the prevention of OHSS when compared with fresh embryo transfer., Search Strategy: Publications in the literature that describe or may describe randomised controlled trials of both human intra-venous albumin and freezing of all embryos in the management of OHSS as consequence of the superovulation in assisted reproduction techniques (ART) cycles were searched. The Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials was searched. In addition, MEDLINE (PUBMED 1985 to 2001), EMBASE (1985 to 2001), CINHAL (1985 to 2001) and the National Research Register were searched, Selection Criteria: Randomised controlled trials (RCTs) in which either human intra-venous albumin or cryopreservation of all embryos were used as a therapeutic approach to OHSS were included. The participants were women of reproductive age who were down regulated by gonadotrophin-releasing hormone-analogue (GnRH-a), undergoing superovulation in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles., Data Collection and Analysis: Two reviewers, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion. Then, both reviewers extracted data independently using forms designed according to Cochrane guidelines. Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing to the corresponding authors directly. The interventions compared were cryopreservation (embryo freezing) versus intra-venous human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil/mild OHSS, clinical pregnancies/woman. The secondary outcomes were: number of oocytes retrieved, number of oocytes fertilized, number of embryos transferred, number of embryos frozen, multiple pregnancy rate, live birth rate, number of women admitted to the hospital as inpatient or outpatient and time to the next menstrual period (resolution time). Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines., Main Results: Seventeen studies were identified, two of which met our inclusion criteria. One study was included where cryopreservation (embryo freezing) was compared with intra-venous human albumin administration (Shaker 1996) and one study was included where elective cryopreservation of all embryos was compared with fresh embryo transfer (Ferraretti 1999). When cryopreservation was compared with intra-venous human albumin administration no difference was found in all the outcomes examined between the two groups. When elective cryopreservation of all embryos was compared with fresh embryo transfer no difference was found in all the outcomes examined between the two groups., Reviewer's Conclusions: This review has showed that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of intra-venous albumin versus cryopreservation.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Its reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and hemoconcentration., Objectives: The objective of this review is to assess the effect of "coasting" (withholding gonadotrophins) as a preventative strategy in the management of OHSS following superovulation in assisted reproduction treatment on the incidence of all clinical grades of OHSS, in comparison with "early unilateral follicular aspiration (EUFA)" or other interventions., Search Strategy: Publications in the literature that described randomised controlled trials (RCTs) in which "coasting" was used as a preventative strategy to OHSS were included. The Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials was searched. In addition, MEDLINE (PUBMED) 1985 to 2002, EMBASE (1985 to 2001), CINHAL (1985 to 2001) and National Research Register were also searched., Selection Criteria: Randomised controlled trials (RCTs) in which coasting was used as a preventative strategy to OHSS were included., Data Collection and Analysis: Two reviewers, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion. Then, both reviewers extracted data independently using forms designed according to Cochrane guidelines. Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing twice to the corresponding authors directly. The interventions compared were "coasting" versus "early unilateral follicular aspiration (EUFA)" or no "coasting" or other interventions. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines., Main Results: This review identified thirteen studies but only one trial met our inclusion criteria. There was no difference in the incidence of moderate and severe OHSS (n=30, OR 0.76, 95% CI 0.18, 3.24)and in the clinical pregnancy rate (n=30, OR 0.75, 95% CI 0.17, 3.33) between the groups., Reviewer's Conclusions: There is a lack of randomised controlled trials for where coasting is compared with no coasting or other interventions such as embryo freezing or intra-venous albumin infusion for prevention of OHSS. There is insufficient evidence to determine if coasting is an effective strategy for preventing OHSS.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS., Objectives: To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome., Search Strategy: The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to November 2001, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers., Selection Criteria: Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review., Data Collection and Analysis: Seven randomised controlled trials were identified, five of which met our inclusion criteria and enrolled 378 women (193 in the albumin treated group and 185 in the control group). Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results.The five included trials were single-centre parallel randomised controlled studies. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention., Data Synthesis: 2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique., Main Results: Meta-analysis of the five included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (odds ratio was 0.28 (95% CI 0.11 to 0.73). Relative risk was 0.35 (0.14 - 0.87) and absolute risk reduction was 5.5. For every 18 women at risk of severe OHSS, albumin infusion will save one more case. There was no evidence of an increase in the pregnancy rate (odds ratio was 1.09, (95% CI 0.65 to 1.83) REVIEWER'S CONCLUSIONS: This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. Whether the NNT would justify the routine use of albumin infusion in cases at risk of severe OHSS needs to be judged by clinical decision makers.

Severe OHSS is an iatrogenic, potentially life-threatening complication of controlled ovarian hyperstimulation. Intravenous human albumin, administered around the time of oocyte retrieval has been claimed to prevent development of this serious event. It was hypothesized that albumin acts through its osmotic pressure and through the binding and inactivation, at a critical time of the cycle, of an hCG-mediated factor secreted by the corpora lutea, that impedes capillary integrity and leads to the development of OHSS. The present article evaluates the available evidence in the medical literature whether albumin is effective in reducing the risk of severe OHSS. Several trials have been identified, most of them were retrospective and few were prospective randomized controlled trials. Although albumin prophylaxis cannot offer absolute protection, all three randomized placebo-controlled trials, that have been published so far, demonstrated a significant reduction in the incidence of severe OHSS.

Background: Approximately 15% of patients with PCOS remain anovulatory despite treatment with oral anti-oestrogen medications such as clomiphene citrate. In addition, about half of women with PCOS ovulating on anti-oestrogen treatment fail to conceive. Gonadotrophin stimulation is the next step in treatment for women who are "clomiphene resistant", however, results of gonadotrophin stimulation in women with PCOS are less successful. In PCOS associated with hypersecretion of LH, purified urinary follicle-stimulating hormone (u-FSH) preparations have theoretical advantages over the use of human menopausal gonadotrophin (hMG) preparations (containing both FSH and LH), but whether this claimed advantage extends into clinical practice remains uncertain. In addition, the use of gonadotrophin-releasing hormone analogues (GnRH-a) to produce pituitary desensitisation prior to ovulation induction in PCOS has been claimed to increase the success rates of treatment as well as reduce complications such as OHSS and multiple pregnancy. Gonadotrophin preparations have also been administered via different routes (intramuscular or subcutaneous), or using different stimulation regimens and protocols (step-up or standard) in an attempt to improve efficacy., Objectives: To determine the effectiveness of urinary-derived gonadotrophins as ovulation induction agents in patients with PCOS trying to conceive. In particular, to assess the effectiveness of (1) different gonadotrophin preparations, (2) the addition of a gonadotrophin-releasing hormone agonist (GnRH-a) to gonadotrophin stimulation and (3) different modalities of gonadotrophin administration., Search Strategy: The search strategy to identify RCTs consisted of (1) the Group's Specialised Register of Controlled Trials using the search strategy developed for the Menstrual Disorders and Subfertility Group as a whole (see the Review Group details for more information), (2) additional specific electronic Medline searches and (3) bibliographies of identified studies and narrative reviews., Selection Criteria: RCTs in which urinary-derived gonadotrophins were used for ovulation induction in patients with primary or secondary subfertility attributable to PCOS., Data Collection and Analysis: Twenty three RCTs were identified, 9 of which were excluded from analysis. The data were extracted independently by 2 authors. The following criteria were assessed: (1) the methodological characteristics of the trials, (2) the baseline characteristics of the studied groups and (3) the outcomes of interest: pregnancy rate (per cycle), ovulation rate (per cycle), miscarriage rate (per pregnancy), multiple pregnancy rate (per pregnancy), overstimulation rate (per cycle) and ovarian hyperstimulation syndrome (OHSS) rate (per cycle). Where suitable, meta-analysis was performed using Peto's OR with 95% CI with the fixed effect Mantel-Haentszel equation., Main Results: (1) A reduction in the incidence of OHSS with FSH compared to hMG in stimulation cycles without the concomitant use of a GnRH-a (OR 0.20; 95% CI 0.08-0.46) and (2) a higher overstimulation rate when a GnRH-a is added to gonadotrophins (OR 3.15; 95% CI 1.48-6.70)., Reviewer's Conclusions: Although 14 RCTs were included in this review, few dealt with the same comparisons, all were small to moderate size and their methodological quality was generally poor. Any conclusions, therefore, remain tentative as they are based on a limited amount of data and will require further RCTs to substantiate them. In none of the comparisons was there a significant improvement in pregnancy rate but this may be due to the lack of power (i.e. insufficient patients randomised to demonstrate a significant difference between treatments). There was a trend towards better pregnancy rates with the addition of a GnRH-a to gonadotrophin stimulation and these interventions warrant further study. Despite theoretical advantages, urinary-derived FSH preparations did not improve pregnancy rates when compared to traditional and cheaper hMG preparations; their only demonstrable benefit was a reduced risk of OHSS in cycles when administered without the concomitant use of a GnRH-a. No conclusions can be drawn on miscarriage and multiple pregnancy rates due to insufficient reporting of these outcomes in the trials.

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS., Objectives: To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome., Search Strategy: The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to the present, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers., Selection Criteria: Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review., Data Collection and Analysis: Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention., Data Synthesis: 2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique., Main Results: Meta-analysis of the three included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (common odds ratio 0.1, 95% confidence interval 0.03 to 0.39). There was no evidence of an increase in the pregnancy rate (common odds ratio 1.69, 95% confidence interval 0.7 to 4.07)., Reviewer's Conclusions: This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. However, the results of this review can not be regarded as conclusive as they are based on only three small trials. Further trials are urgently needed.

Objectives: To define the incidence and severity of ovarian hyperstimulation syndrome (OHSS) occurring in oocyte donors., Methods: Women (n = 149) aged 31.3 +/- 4.8 years (mean +/- S.D., range 21-41 years) participated as designated oocyte donors and underwent 400 consecutive cycles of controlled ovarian stimulation using human menopausal gonadotropin following pituitary downregulation with gonadotropin-releasing agonist. Patients were monitored by serial transvaginal ultrasound examinations and serum estradiol (E2) determinations. Oocytes (15.6 +/- 7.5 per aspiration; range 2-57) were harvested by ultrasound-directed transvaginal follicle aspiration 36 h following the intramuscular injection of human chorionic gonadotropin (hCG). Follow-up examination occurred 1 and 2 weeks post-aspiration., Results: On the day of hCG injection E2 levels ranged from 512 to 13,502 pg/ml (mean 2902.7 +/- 1486.9 pg/ml). Over the next few weeks the degree of hyperstimulation in donors was staged: mild 65% (grade I, n = 98; grade II, n = 162); moderate 33.5% (grade III, n = 120; grade IV, n = 14); severe 1.5% (grade V, n = 6; grade VI, n = 0). Associated preaspiration E2 levels were: grade I, 1120 +/- 424 pg/ml; grade II, 2084 +/- 613 pg/ml; grade III, 3785 +/- 1713 pg/ml; grade IV, 5370 +/- 1264 pg/ml; grade V, 4286 +/- 1100 pg/ml. Worsening OHSS was associated with increasing levels of E2. There were no serious complications and hospitalization was not required. All symptoms resolved within 30 days of aspiration, disappearing by the time of the first menstrual flow in women of grade-III or lower stage., Conclusion: Although oocyte donors commonly experienced exaggerated levels of serum E2 they rarely (< 2%) developed severe OHSS. This may be attributable to their lack of embryo transfer which avoids exacerbating the illness.