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The assessments of oocyte quality and quantity and endocrine profile have traditionally been the cornerstone of the general workup of couples with infertility. Over the years, several clinical, hormonal, and functional biomarkers have been adopted to assess ovarian function and identify endocrine disorders before assisted reproductive technology. Furthermore, the genetic workup of patients has drastically changed, introducing novel markers. This not only allowed the prediction of response to ovarian stimulation but also contributed toward the development of a safer and more efficient management of women undergoing assisted reproductive technology. The scope of this review is to provide an overview of the current and novel strategies adopted for the assessment of ovarian function and ovulatory and endocrine disorders in women planning to conceive. Furthermore, it aims to provide an insight in the role of novel genetic biomarkers and use of expanded carrier screening as part of preliminary workup of women with infertility. [ABSTRACT FROM AUTHOR]

Study Question: Does the presence of single nucleotide polymorphisms (SNPs) in the FSH receptor gene (FSHR) and/or FSH beta subunit-encoding gene (FSHB) influence ovarian response in predicted normal responders treated with rFSH?Summary Answer: The presence of FSHR SNPs (rs6165, rs6166, rs1394205) has a statistically significant impact in ovarian response, although this effect is of minimal clinical relevance in predicted normal responders treated with a fixed dose of 150 IU rFSH.What Is Known Already: Ovarian reserve markers have been a breakthrough in response prediction following ovarian stimulation. However, a significant percentage of patients show a disproportionate lower ovarian response, as compared with their actual ovarian reserve. Studies on pharmacogenetics have demonstrated a relationship between FSHR or FSHB genotyping and drug response, suggesting a potential effect of individual genetic variability on ovarian stimulation. However, evidence from these studies is inconsistent, due to the inclusion of patients with variable ovarian reserve, use of different starting gonadotropin doses, and allowance for dose adjustments during treatment. This highlights the necessity of a well-controlled prospective study in a homogenous population treated with the same fixed protocol.Study Design, Size, Duration: We conducted a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium, and Spain (168 from Europe and 200 from Asia), from November 2016 until June 2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonist protocol with a fixed daily dose of 150 IU rFSH until triggering. Blood sampling and DNA extraction was performed prior to oocyte retrieval, followed by genotyping of four SNPs from FSHR (rs6165, rs6166, rs1394205) and FSHB (rs10835638).Participants/materials, Setting, Methods: Eligible were predicted normal responder women <38 years old undergoing their first or second ovarian stimulation cycle. Laboratory staff and clinicians were blinded to the clinical results and genotyping, respectively. The prevalence of hypo-responders, the number of oocytes retrieved, the follicular output rate (FORT), and the follicle to oocyte index (FOI) were compared between different FSHR and FSHB SNPs genotypes.Main Results and the Role Of Chance: The prevalence of derived allele homozygous SNPs in the FSHR was rs6166 (genotype G/G) 15.8%, rs6165 (genotype G/G) 34.8%, and rs1394205 (genotype A/A) 14.1%, with significant differences between Caucasian and Asian women (P < 0.001). FSHB variant rs10835638 (c.-211 G>T) was very rare (0.5%). Genetic model analysis revealed that the presence of the G allele in FSHR variant rs6166 resulted in less oocytes retrieved when compared to the AA genotype (13.54 ± 0.46 vs 14.81 ± 0.61, estimated mean difference (EMD) -1.47 (95% CI -2.82 to -0.11)). In FSHR variant rs1394205, a significantly lower number of oocytes was retrieved in patients with an A allele when compared to G/G (13.33 ± 0.41 vs 15.06 ± 0.68, EMD -1.69 (95% CI -3.06 to -0.31)). A significantly higher prevalence of hypo-responders was found in patients with the genotype A/G for FSHR variant rs6166 (55.9%, n = 57) when compared to A/A (28.4%, n = 29), ORadj 1.87 (95% CI 1.08-3.24). No significant differences were found regarding the FORT across the genotypes for FSHR variants rs6166, rs6165, or rs1394205. Regarding the FOI, the presence of the G allele for FSHR variant rs6166 resulted in a lower FOI when compared to the A/A genotype, EMD -13.47 (95% CI -22.69 to -4.24). Regarding FSHR variant rs6165, a lower FOI was reported for genotype A/G (79.75 ± 3.35) when compared to genotype A/A (92.08 ± 6.23), EMD -13.81 (95% CI -25.41 to -2.21).Limitations, Reasons For Caution: The study was performed in relatively young women with normal ovarian reserve to eliminate biases related to age-related fertility decline; thus, caution is needed when extrapolating results to older populations. In addition, no analysis was performed for FSHB variant rs10835638 due to the very low prevalence of the genotype T/T (n = 2).Wider Implications Of the Findings: Based on our results, genotyping FSHR SNPs rs6165, rs6166, rs1394205, and FSHB SNP rs10835638 prior to initiating an ovarian stimulation with rFSH in predicted normal responders should not be recommended, taking into account the minimal clinical impact of such information in this population. Future research may focus on other populations and other genes related to folliculogenesis or steroidogenesis.Study Funding/competing Interest(s): This study was supported by an unrestricted grant by Merck Sharp & Dohme (MSD). N.P.P. reports grants and/or personal fees from MSD, Merck Serono, Roche Diagnostics, Ferring International, Besins Healthcare, Gedeon Richter, Theramex, and Institut Biochimique SA (IBSA). N.L.V. and M.T.H. report consultancy and conference fees from Merck, Ferring, and MSD, outside the submitted work. P.D. has received honoraria for lecturing and/or research grants from MSD, Ferring International, and Merck. D.S. reports grants and/or personal fees from MSD, Ferring International, Merck Serono, Cook, and Gedeon Richter. A.R.N., B.A.M., C.S., J.M., L.H.L., P.Q.M.M., H.T., and S.G. report no conflict of interests.Trial Registration Number: NCT03007043. [ABSTRACT FROM AUTHOR]

Study Question: Does the timing of the first frozen embryo transfer (FET) after gonadotropin-releasing hormone (GnRH) agonist triggering with the elective cryopreservation of all embryos affect pregnancy outcome?Summary Answer: FETs performed immediately after a freeze-all cycle did not vary significantly from delayed FETs in terms of pregnancy rates.What Is Known Already: As interest in, and use of, the freeze-all strategy expands in the field of reproductive medicine, the optimal timing to perform the subsequent FET has become increasingly important. Thus far, all clinical trials evaluating the efficacy of the segmentation strategy have opted to electively defer the first FET for at least one menstrual cycle. However, this mere empirical approach may cause unnecessary distress to infertile patients eager to conceive as soon as possible.Study Design, Size and Duration: This retrospective cohort study included the first FET cycle of all women who underwent a freeze-all protocol between October 2010 and October 2015 in two reproductive medicine centres (in Belgium and Vietnam, respectively).Participants/materials, Setting and Methods: A total of 333 FET cycles were included in the analysis. Following the freeze-all cycle, the preparation of the endometrium consisted of the sequential administration of oestradiol valerate and micronized vaginal progesterone. The start of the FET was classified as either immediate (following the GnRH agonist withdrawal bleeding) or delayed (by at least one menstrual cycle). Clinical pregnancy rate (CPR) was the main outcome of our study.Main Results and the Role Of Chance: Women in the immediate FET group were slightly younger on average (30.9 ± 4.1 versus 31.8 ± 4.3, P = 0.045) on the date of oocyte retrieval. Moreover, women in the immediate FET group received a blastocyst transfer more frequently (53.4% versus 41.6%, P = 0.038) and had fewer embryos transferred on average compared to the delayed FET group (1.8 ± 0.8 versus 2.0 ± 0.8, P = 0.013). CPR/FET was marginally significantly higher in the immediate FET group in our crude analysis (52.9% after immediate FET versus 41.6% after delayed FET, P = 0.046). In order to assess if CPR/FET remained unaltered after adjusting for measured confounding, we performed mixed-effects multivariable regression analysis. Timing of the FET no longer affected significantly the CPR of the first FET in the adjusted analysis (adjusted odds ratio (aOR): 0.62, 95% CI: 0.38-1.00; predicted CPR of 52.5% for immediate FET versus 41.8% for delayed FET).Limitations, Reasons For Caution: The results are limited by the retrospective design and the potential for unmeasured confounding. Furthermore, we only evaluated the effect of the FET timing of the first FET on CPRs in artificially supplemented cycles and, thus, the results should not be extrapolated to live birth rates or natural-cycle FETs.Wider Implications Of the Findings: This study offers a simple but potentially relevant measure to increase patient satisfaction and adherence in couples who seek to become pregnant both safely and as soon as possible.Study Funding/competing Interests: No funding was received for this study. The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 μg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (<40 years old) and 12% in older women (≥40 years old),p = 0.68. Similarly, in patients treated with the long agonist protocol younger women had an OPR of 26.7% versus 12.5% in older women,p = 0.23. Among patients treated with the short flare-up, live births rate were 15% and 4.3% for younger (<40 years old) and older patients (≥40 years old), respectively,p = 0.32. Similarly, in patients treated with the long agonist protocol, live births rate were 25% and 12.9% for younger (<40 years old) and older patients (≥40 years old), respectively,p = 0.41. None of the patients reported any serious adverse event related to treatment. According to our results, CFA followed by hpHMG in a short flare-up or long GnRH agonist protocol appears to be a feasible option for poor ovarian responders. Large phase III trials are mandatory prior to introduction in clinical practice. 在两个前瞻性非控制的可行性试验中，检测对卵巢低反应妇女应用绒促卵泡素a (CFA)后应用高纯人绝经期促性腺激素（hpHMG），比较短期flare- up促性腺激素释放激素(GnRH)激动剂方案和GnRHa长方案的效果。总体，45名患者应用短期flare- up方案，47名患者应用GnRHa长方案。所有患者应用单剂量150 μg CFA，7天后应用300IU hpHMG，10000 IUhCG触发排卵，CSI和3天胚胎移植。持续妊娠率（OPRs），GnRHa短期方案的15.6%和长方案的17%间没有差异(p=0.85)。在应用短期flare-up方案的患者中，OPRs在年轻患者(<40岁)为20%，高龄患者(≥40岁)为12%，p=0.68。同样的在应用GnRHa长方案的患者中，年轻妇女OPR为26.7%，高龄妇女为12.5%, p= 0.23。在应用短期flare-up方案的患者中，年轻患者(<40岁)活产率为15%，高龄患者(≥40岁)活产率为4.3%，p=0.32。同样的，在GnRHa长方案的患者中，年轻患者(<40岁)活产率为25%，高龄患者(≥40岁)活产率为12.9%，p=0.41。没有患者报告有与治疗相关的不良事件。根据结果，在的短期flare- up方案或者GnRHa长方案中应用CFA后序贯hpHMG对卵巢低反应患者是可行性的选择。在引入临床实践前还必须有大型III期试验。 [ABSTRACT FROM PUBLISHER]

Background. Triggering final oocyte maturation is a key step of ovarian stimulation. Although previous studies demonstrated a negative association between female BMI and serum hCG levels, little evidence is available regarding the association between oocyte yield and patients' BMI. The scope of the current study was to examine whether the efficiency of the r-hCG and triptorelin to trigger final oocyte maturation may be associated with patients' BMI or weight. Methods. This is a retrospective observational study including 5190 ovarian stimulation cycles performed between January 2019 and September 2022 in the Reproductive Medicine Department of Dexeus University Hospital. Cycles were analyzed according to the type of trigger (triptorelin vs. r-hCG vs. dual). The primary outcome measures were oocyte maturation rate (MII/oocytes) and FOI (oocytes/AFC); secondary outcomes were oocyte and MII yield. Results. Multivariable regression analysis, adjusting for confounding factors, demonstrated that BMI was not associated with oocyte maturation rate (OR: 1.00 [95%CI: 0.99; 1.01]), FOI (Beta 0.52 [95%CI: −0.49; 1.54]), number of oocytes (Beta 0.02 [95%CI: −0.08; 0.13]) or MIIs (Beta 0.01 [95%CI: −0.08; 0.10]) retrieved. Similarly, all analyses conducted considering patients' weight failed to reveal any association. Conclusion. Our study demonstrates that, independent of the type of trigger, patients' BMI and weight are not associated with oocyte yield, maturation, or FOI. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: IS there any association between thyroid autoimmunity (TAI) and diminished ovarian reserve (DOR)? SUMMARY ANSWER: TAI and hypothyroidism are not associated with low ovarian reserve. WHAT IS KNOWN ALREADY: TAI is a common co-existent endocrinopathy in women with primary ovarian insufficiency. Several studies support a potential link between TAI and the reduction in ovarian reserve. However, robust evidence regarding its prevalence in women with DOR is lacking. STUDY DESIGN, SIZE, DURATION: This study is a large cross-sectional analysis of retrospective data from the Centre for Reproductive Medicine/University Hospital of Brussels. Serum measurements were taken for anti-Mullerian hormone (AMH), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroperoxidase (anti-TPO). PARTICIPANTS/MATERIALS, SETTING, METHODS: Among 5076 consecutive women, 4894 women had their AMH, FT4,TSH and anti-TPO levels measured on the same day. AMH levels were plotted in relation to age for the whole patients' cohort and age-specific AMH values (per year) were considered in order to categorize women according to the AMH levels of ovarian reserve. There were 3929 women who demonstrated normal reserve, 487 women who had low ovarian reserve and 478 women who demonstrated high ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: Serum FT4 and TSH levels were comparable between different ovarian reserve categories (P = 0.61 1 and 0.81 1, respectively). No significant differences were observed in the prevalence of positive anti-TPO antibodies among women with low (12.1%), normal (10.3%) and high (9.8%) ovarian reserve (P = 0.423). Finally, the prevalence of overt or subclinical hypothyroidism was comparable between the groups (4.1 % in low, 4.6% in normal and 3.8% in high ovarian reserve women, P = 0.645). Analysis according to the exact cause of low ovarian reserve demonstrated that women with a genetic cause of low ovarian reserve had a significantly higher prevalence of overt hypothyroidism and subclinical hypothyroidism compared with women with unexplained low ovarian reserve for their age (25 versus 3.2%, P = 0.002 and 18.8 versus 1.6%, P = 0.004, respectively). On the contrary, no significant differences were observed in the prevalence of hypothyroidism between genetic causes and iatrogenic causes (P = 0.3 16) and between iatrogenic and unexplained causes (P= 0.219) of low ovarian reserve. LIMITATIONS, REASONS FOR CAUTION: This is a cross-sectional analysis based on retrospective data collection. Due to the retrospective design of this study, the presence of biases related to such a study design cannot be excluded. Furthermore, this study assessed only the association of TAI, and not autoimmunity in general, with ovarian reserve. WIDER IMPLICATIONS OF THE FINDINGS: TAI and hypothyroidism are not associated with low ovarian reserve. Future research should focus on examining underlying mechanisms, other than TAI, which may have an effect on ovarian reserve. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the influence of vitamin D deficiency on pregnancy rates among women undergoing IVF/ICSI and Day 5 (blastocyst stage) single embryo transfer (SET)? SUMMARY ANSWER Vitamin D deficiency results in significantly lower pregnancy rates in women undergoing single blastocyst transfer. WHAT IS KNOWN ALREADY Preliminary experiments have identified the presence of vitamin D receptors in the female reproductive system. However, results regarding the effect of vitamin D deficiency on clinical outcomes are conflicting. None of the previous studies adopted a SET strategy. STUDY DESIGN, SIZE, DURATION Serum vitamin D concentration was measured retrospectively in patients who underwent SET on Day 5. Overall 368 consecutive infertile women treated within a period of 15 months were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients underwent ovarian stimulation for IVF/ICSI and Day 5 SET. Serum samples were obtained 7 days prior to embryo transfer and stored frozen at −20°C. Samples were collectively analyzed for their 25-OH vitamin D content. Vitamin D deficiency was defined as serum 25-OH vitamin D levels <20 ng/ml in accordance with the Institute of Medicine and the Endocrine Society clinical practice guidelines. MAIN RESULTS AND THE ROLE OF CHANCE Clinical pregnancy rates were significantly lower in women with vitamin D deficiency compared with those with higher vitamin D values (41 versus 54%, P = 0.015).Logistic regression analysis was performed to identify whether vitamin D deficiency is independently associated with clinical pregnancy rates after controlling for 16 potential confounding factors. According to our results vitamin D deficiency was independently associated with lower clinical pregnancy rates, odds ratios [ORs (95% confidence interval (CI) 0.61 (0.39–0.95)] for vitamin D deficiency (deficient versus non-deficient women), P = 0.030. Finally, even when restricting our analysis to women undergoing elective SET (274 patients), vitamin D deficiency was again independently associated with pregnancy rates [OR (95% CI) 0.56 (0.33–0.93), P = 0.024]. LIMITATIONS, REASONS FOR CAUTION Our results refer only to patients undergoing Day 5 SET. Although vitamin D deficiency appears to compromise pregnancy rates in this population, no guidance can be provided regarding a potential relationship between vitamin D deficiency and ovarian reserve or response to ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS Vitamin D deficiency impairs pregnancy rates in women undergoing single blastocyst transfer. Future prospective confirmatory studies are needed to validate our results and examine the exact underlying mechanism by which vitamin D levels may impair pregnancy rates in infertile women undergoing IVF/ICSI. STUDY FUNDING/COMPETING INTEREST(S) None declared. [ABSTRACT FROM PUBLISHER]

This retrospective study determined the efficacy of ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI) in poor ovarian responders fulfilling the Bologna criteria for poor ovarian response and identified predictors of live birth rates. Overall, 485 patients undergoing 823 ovarian stimulation cycles for IVF/ICSI with maximum gonadotrophin dose (≥300 IU) between January 2009 and December 2011 were included. Patients were considered eligible, irrespective of the treatment protocol, if they were classified as poor responders based on the recently developed definition for poor ovarian response by the European Society of Human Reproduction and Embryology, the Bologna criteria. Live birth rates did not significantly differ between women aged <40 and women aged ≥40 years either per cycle (7.1 versus 5.2%, OR 1.38, 95% CI 0.77-2.46) or per patient (11.6 versus 8.8%, OR 1.36, 95% Cl 0.75-2.46). In logistic regression analysis, the number of oocytes retrieved was the only variable significantly associated with live births (OR 1.92, 95% CI 1.03-3.55 for >3 versus 1-3 oocytes). Bologna poor responders demonstrate very low live birth rates, irrespective of age and treatment protocol used. An increase in the number of oocytes retrieved is an independent variable related to live birth rates. [ABSTRACT FROM AUTHOR]

Background To examine whether ovarian puncture for immature oocyte retrieval and in-vitro maturation (IVM) has an effect on the endocrine profile of patients with polycystic ovary syndrome (PCOS). Methods Twenty-two consecutive patients with PCOS undergoing IVM treatment were included. Serum anti-Müllerian hormone (AMH), sex hormone-binding globulin (SHBG), total testosterone (TT) and luteinized hormone (LH) levels were analyzed at the start of the cycle, on the day of immature oocyte retrieval (OR) and at fixed intervals thereafter, for up to three months after OR. Results Five days after OR circulating AMH, TT, calculated free testosterone (FTc), and LH levels were significantly reduced and circulating SHBG was significantly increased. Two weeks after OR, TT, FTc and LH remained reduced, whereas circulating AMH and SHBG levels recovered to pre-puncture values. Three months after OR, all circulating hormone levels had recovered to baseline values. Conclusion Ovarian puncture for the retrieval of immature oocytes and IVM in patients with PCOS has a significant impact on the ovarian endocrine profile, but this impact is brief and transient. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the time interval between serum antimüllerian hormone (AMH) sampling and initiation of ovarian stimulation for in vitro fertilization–intracytoplasmic sperm injection (IVF-ICSI) may affect the predictive ability of the marker for low and excessive ovarian response. Design: Retrospective cohort study. Setting: University-based tertiary center. Patient(s): Five hundred and forty women with AMH values measured before their first IVF-ICSI cycle. Intervention(s): Eligible patients treated with 150–225 IU recombinant follicle-stimulating hormone (FSH) in a gonadotropin-releasing hormone (GnRH) antagonist protocol. Main Outcome Measure(s): Predictive ability of AMH for low and excessive ovarian response in relation to the time interval between serum AMH sampling and initiation of ovarian stimulation for IVF-ICSI. Result(s): All patients had their AMH concentration measured up to 12 months before initiation of stimulation. The level of AMH demonstrated a statistically significant positive correlation with number of oocytes retrieved. The time interval between AMH measurement and initiation of stimulation had no influence on this correlation. The area under the receiver operator characteristic curve (ROC AUC) of AMH was high for both poor (0.72) and excessive response (0.80). The ROC regression analysis demonstrated that the time interval from sampling did not affect the performance of either poor response or excessive response prediction. Conclusion(s): A time interval up to 12 months between AMH serum sampling and initiation of ovarian stimulation does not appear to affect the correlation between AMH level and the number of oocytes retrieved and the predictive ability of AMH to identify women at risk of low or excessive ovarian response. [ABSTRACT FROM AUTHOR]

Objective: To identify predictors of ovarian response in women undergoing ovarian stimulation with corifollitropin alfa in a GnRH antagonist protocol and determine specific thresholds for the prediction of low and excessive responders. Design: Retrospective cohort study. Setting: University-based tertiary care center. Patient(s): Infertile women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection. Intervention(s): Controlled ovarian hyperstimulation with corifollitropin alfa in a GnRH antagonist protocol. Main Outcome Measure(s): Relationship between ovarian reserve tests and ovarian response. Result(s): Antimüllerian hormone (AMH) and antral follicle count (AFC) were the only independent predictors for low and excessive ovarian response. In prediction of excessive response, the area under the receiver operating characteristic curve [AUC (95% CI)] for AMH was 0.890 (0.832–0.947) and 0.897 (0.829–0.964) for AFC. The optimal thresholds for identifying excessive responders were 3.52 ng/mL for AMH (sensitivity 89.5, specificity 83.8) and 16 for AFC (sensitivity 80.0, specificity 84.5). AMH and AFC also predicted low ovarian response: AUCs AMH 0.836 (0.783–0.889) and AFC 0.830 (0.767–0.894). The optimal thresholds for predicting low response were 1.37 ng/mL for AMH (sensitivity 74.1, specificity 77.5) and 8 for AFC (sensitivity 72.2, specificity 84.6). For both excessive and low ovarian responses, a logistic regression model combining the biomarkers was associated with improved discrimination. Conclusion(s): AMH and AFC are the best predictors for low and excessive response in women treated with corifollitropin alfa in an antagonist protocol. Using AMH and AFC to select suitable candidates for treatment with corifollitropin alfa may result in a safe and convenient stimulation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the reproductive outcome in patients receiving frozen-thawed embryo transfer before and after doubting of the vaginal progesterone gel supplementation. The study was a retrospective study performed in The Fertility Clinic, Skive Regional Hospital, Denmark. A total of 346 infertility patients with oligoamenorrhoea undergoing frozen-thawed embryo transfer after priming with oestradiol and vaginal progesterone get were included. The vaginal progesterone dose was changed from 90 mg (Crinone) once a day to twice a day and the reproductive outcome during the two periods was compared. The pregnancy rate increased significantly after doubting of the progesterone dose (26.7% (90 mg) versus 38.4% (180 rag); P = 0.021). Moreover, the early pregnancy loss rate decreased significantly (67.4% versus 43.7%, respectively; P = 0.014), which significantly increased the delivery rate (8.7% versus 20.5%, respectively; P = 0.002). Doubting of the vaginal progesterone get supplementation during frozen-thawed embryo transfer cycles decreased the early pregnancy toss rate, resulting in a significantly higher delivery rate. [ABSTRACT FROM AUTHOR]

Objective: To identify whether women with poor ovarian response may benefit from treatment with corifollitropin alfa in a GnRH antagonist protocol. Design: Retrospective pilot study. Setting: University-based tertiary care center. Patient(s): Poor ovarian responders fulfilling the Bologna criteria developed by European Society for Human Reproduction and Embryology Consensus Group. Intervention(s): Corifollitropin alfa (150 μg) followed by 300 IU rFSH in a GnRH antagonist protocol. Main Outcome Measure(s): Endocrinologic profile and ongoing pregnancy rates. Result(s): Among 43 women treated with corifollitropin alfa, mean E2 levels showed an increasing pattern during the follicular phase, reaching 825 ng/L on the day of hCG administration, whereas FSH values showed a marked increase during the first 5 days, reaching a mean value of 35 IU/L and remaining above 20 IU/L during the late follicular phase. Cycle cancellation rate was 32.6% and embryo transfer rate 53.3%. Five patients (11.7%) had a positive hCG test and three (7%) had an ongoing pregnancy. Ongoing pregnancy rates were 11.1% per oocyte retrieval and 13% per embryo transfer. Ongoing pregnancy rates per patient did not significantly differ compared with a cohort of patients treated during 2011 with the standard protocol for poor responders in our center (short agonist-hMG) (7% vs. 6.3%). Conclusion(s): Treatment of poor ovarian responders, as described by the Bologna criteria, with corifollitropin alfa in a GnRH antagonist protocol results in low pregnancy rates, similarly to conventional stimulation with a short agonist protocol. [ABSTRACT FROM AUTHOR]

Evidence regarding the role of anti-Müllerian hormone (AMH) among oocyte donors is limited and only involves gonadotrophin-releasing hormone (GnRH)-agonist-treated donors. This trial assessed the predictive ability of AMH for ovarian response among 108 oocyte donors treated with an antagonist protocol. In multivariate linear regression analysis, both AMH and age were independently associated with ovarian response (unstandardized coefficients 0.904 and -0.378, respectively). In receiver operating characteristic curve analysis, AMH performed better than age, but was a modest predictive marker for low (≤6 oocytes) and excessive (>20 oocytes) ovarian response (area under the curve (AUC) 0.643 and 0.695, respectively). Similarly, a multivariate logistic model including AMH and age was also modest (AUC 0.651 and 0.697 for low and excessive responders, respectively). The predictive ability of AMH did not significantly alter when different thresholds were adopted, such as <4 oocytes for low response and >25 for excessive response (AUC 0.759 and 0.724, respectively). Among oocyte donors treated with a GnRH-antagonist protocol, although AMH was correlated with the number of oocytes retrieved, it demonstrates a modest ability in discriminating women with low or excessive ovarian response. [ABSTRACT FROM AUTHOR]

Published data indicate a significant increase in ovarian hyperstimulation syndrome globally. The occurrence of approximately three maternal deaths per 100 000 stimulated women has been reported, and extrapolation of these figures to a global situation would give an impressive number. The syndrome can be erased by applying ovarian stimulation using the combination of GnRH antagonist with GnRH agonist to trigger ovulation. In this case, the strategy is to freeze all of the oocytes or embryos for later use. [ABSTRACT FROM PUBLISHER]

BACKGROUND Treatment decisions should ideally be based on well-designed randomized controlled trials (RCTs). Here we determine the rate of full publication of RCTs presented at annual meetings of the European Society of Human Reproduction and Embryology (ESHRE), identify potential bias against publishing non-significant results and results not favoring the experimental arm, quantify this bias in case it exists, and identify factors associated with time to publication. METHODS RCTs presented at ESHRE meetings 2003 and 2004 were recorded. Subsequent search in Medline, Cochrane Library and EMBASE was performed through December 2010 to identify full-text publication in a peer-review journal. RESULTS Among 155 abstracts describing RCTs 89 (57%) were published in full-text in a peer-review journal. Median time from presentation to publication was 15 months (range: 0–75). In bivariate analysis, only type of presentation and presence of outcomes favoring the experimental arm were related to publication rate. Studies presented orally or reporting a positive outcome in favor of the experimental arm were more likely to be published (P = 0.018 and 0.014, respectively). Results were consistent in a multivariable logistic regression, with odds ratio (OR) 2.51 [95% confidence interval (CI), 1.25–5.03] for oral versus poster presentations and OR 2.46 (95% CI, 1.23–4.95) for trials favoring versus not favoring the experimental arm. Kaplan–Meier curves revealed time to publication was shorter for oral presentations (log-rank test = 0.013) and trials favoring the experimental arm, compared with all others (log rank = 0.007). CONCLUSIONS RCTs with significant results in favor of the experimental arm are more likely to be published and are published sooner. Publication bias in reproductive medicine is a fact. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. Methods: We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. Results: Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. Conclusions: Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence. [ABSTRACT FROM AUTHOR]

Background: Industry involvement has been associated with more favourable cost-effectiveness ratios in cost-effectiveness analyses, but the mechanisms for this association are unclear. We evaluated whether the assumed accuracy of the Papanicolaou (Pap) test was correlated with the features of cost-effectiveness analysis studies. Methods: We searched PubMed (last updated April 2010) for cost-effectiveness analysis studies in which at least one strategy involved the Pap test for cervical cancer. We assessed the baseline assumed diagnostic sensitivity and specificity of the Pap test in each study and the association of these values with three levels of manufacturer involvement in the study. Results: Among 88 analyzed cost-effectiveness analysis studies, the assumed sensitivity of the Pap test was lower in studies with manufactureraffiliated authors, manufacturer funding or manufacturer-related competing interests versus studies without (mean sensitivity 60% v. 70%, p < 0.001). The assumed specificity of the Pap test was lower in cost-effectiveness analyses involving new screening tests (mean 93% v. 96%, p = 0.016). The assumed specificity did not differ between trials with manufacturer involvement versus those without (mean 95% v. 95%, p = 0.755). Interpretation: The results of cost-effectiveness analyses may be affected by a downgrading of the assumed diagnostic accuracy of the standard Pap test against which newer tests or interventions are compared. New technology then seems to have more favourable results against a straw-man comparator. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether vaginal progesterone gel may result in similar or higher pregnancy rates compared with all other vaginal progesterone forms when used for luteal-phase support. Design: Meta-analysis of randomized controlled trials using odds ratios (OR) and 95% confidence intervals (CI). Patient(s): Infertile women undergoing IVF or ICSI. Intervention(s): Vaginal progesterone gel 90mg once or twice daily versus any other vaginal progesterone form for luteal phase support. Main Outcome Measure(s): Clinical pregnancy rates. Result(s): Seven randomized controlled trials, involving 2,447 patients, were included in the analysis. No difference was observed in the overall clinical pregnancy rate when comparing vaginal progesterone gel with any other vaginal progesterone form. Moreover, clinical pregnancy rates were similar in protocols using only GnRH agonists and when comparing vaginal gel with the traditional treatment of 200 mg × 3 vaginal progesterone capsules. Conclusion(s): This meta-analysis provides solid evidence that no significant difference exists between vaginal gel and all other vaginal progesterone forms in terms of clinical pregnancy rates. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of double versus single intrauterine insemination (IUI) per treatment cycle in women with unexplained infertility.Design: Meta-analysis of randomized controlled trials.Main Outcome Measure(s): Clinical pregnancy rates per couple.Intervention(s): Electronic searches of the Cochrane Central Trials Registry and Medline without year and language restriction through March 2009; hand searching of the abstract books of the European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine annual meetings (2001-2008).Result(s): Six randomized trials, involving 829 women, were included in the analysis. Fifty-four (13.6%) clinical pregnancies were recorded for treatment with double IUI and 62 (14.4%) for treatment with single IUI. There was no significant difference between the single and double IUI groups in the probability for clinical pregnancy (odds ratio, 0.92; 95% confidence interval, 0.58-1.45; P=0.715).Conclusion(s): Double IUI offers no clear benefit in the overall clinical pregnancy rate in couples with unexplained infertility. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Recent data suggest that fractures might affect quality of life and survival in early breast cancer patients. Bisphosphonates are effective in treatment and prevention of cancer treatment-induced bone loss, but their value in the prevention of fractures is still investigational. Our aim was to evaluate the fracture rate in breast cancer patients receiving adjuvant bisphosphonates compared with those receiving no treatment or placebo. Methods: Our study is a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library and major cancer scientific meetings searches. We identified 21 potentially eligible trials. Of these, 14 studies reported fracture data and were included in the analyses. Overall, 7461 early breast cancer patients were randomized, 3691 received bisphosphonates and 3770 received either placebo or no treatment. Results: Adjuvant breast cancer treatment with bisphosphonates did not reduce the fracture rate compared to placebo or no use either in intent to treat analysis (12 trials, OR=0.99, 95% CI=0.73–1.34, p =0.932) and in comprehensive analysis (all 14 trials included, OR=0.84, 95% CI=0.65–1.09 p =0.197). Treatment with bisphosphonates was not beneficial in postmenopausal patients (7 trials, OR=0.82, 95% CI=0.55–1.20 p =0.298) and in patients receiving aromatase inhibitors (6 trials, OR=0.79, 95% CI=0.53–1.17 p =0.242). Conclusion: Our meta-analysis provides substantial evidence that bisphosphonates in the adjuvant setting among women with breast cancer do not decrease the number of fractures compared with placebo or no treatment. [Copyright &y& Elsevier]

Ovulation induction remains a milestone in the treatment of women with anovulatory infertility. Clomiphene citrate (CC) is considered the first line treatment for induction of ovulation in women with polycystic ovary syndrome (PCOS), while it may be used for ovulation induction in unexplained infertility. Aromatase inhibitors (AI) have been introduced as a new treatment option that could challenge CC for ovulation induction. A systematic review of the literature was conducted in order to highlight the efficacy and safety of AI in female infertility. Current data from randomized and non-randomized trials suggest that AI may have a role in ovulation induction regimens in PCOS patients, as well as for ovarian stimulation, since they achieve comparable clinical pregnancy rates to CC. Furthermore, when combined with gonadotrophins, AI improve the ovarian response of poor responders and reduce the gonadotrophin dose required. However, the current review is based on small trials with a limited number of patients. If solid data from future large adequately powered randomized trials support current evidence regarding efficacy and safety, AI might offer a new treatment choice for infertile women. [ABSTRACT FROM AUTHOR]

Background. Many systemic nonhormonal regimens have been evaluated across several hundreds of randomized trials in advanced breast cancer. We aimed to quantify the relative merits of these regimens in prolonging survival. Method.s We performed a systematic review of all trials that compared different regimens involving chemotherapy and/or targeted therapy in advanced breast cancer (1973-2007). Regimens were categorized a priori into different treatment types. We performed multiple-treatments meta-analysis and calculated hazard ratios for each treatment category relative to monotherapy with old agents (ie, regimens not including anthracydines, anthracenediones, vinorelbine, gemcitabine, capecitabine, taxanes, marimastat, thalidomide, trastuzumab, lapatinib, or bevacizumab). Results. We identified 370 eligible randomized trials (54189 patients), of which 172 (31 552 patients) compared different types of treatment. Survival data from 148 comparisons pertaining to 128 of the 172 trials (26031 patients, 22 different types of treatment) were available for inclusion in the multiple-treatments metaanalysis. Compared with single-agent chemotherapy with old nonanthracycline drugs, anthracycline regimens achieved 22%-33% relative risk reductions in mortality (ie, hazard ratio [HR] for standard-dose anthracycline-based combination: 0.67, 95% credibility interval [Cr1] 0.57-0.78). Several newer regimens achieved further benefits (eg, HR [95% Cr1] 0.67 [0.55-0.81] for single-drug taxane, 0.64 [0.53-0.78] for combination of anthracyclines with taxane, 0.49 [0.37-0.67] for taxane-based combination with capecitabine or gemcitabine), and similar benefits were seen with several regimens including molecular targeted treatments. Most regimens had very similar efficacy profiles (<5% difference in HR) as firstand subsequentline therapies. Conclusions. Stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer. Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles. [ABSTRACT FROM AUTHOR]

Abstract: We examined the interpretation of research findings and public availability of transparent information on data and processing for 46 articles of microarray studies that had addressed major cancer outcomes. Unsupervised and supervised methods selected molecular signatures with a median of 675 and 50 genes, respectively, but only a median of eight genes or groups thereof were further discussed. Across 479 genes or groups thereof discussed in all 46 studies, 65% reflected specific comments (reflecting external relevant data from other studies or other lines of reasoning relevant to the gene of interest), and 59% of the comments were referenced. Among specific comments, supportive ones outnumbered comments against the research findings by nine to one (270 versus 29). Discussion was similarly selective in early studies and in studies published in 2006. Even in 2006 only 10 of 15 studies had publicly deposited data. Only three studies had scanned images, raw and processed data available. Processing details varied. Public transparency and unbiased interpretation of findings can be improved in microarray research. [Copyright &y& Elsevier]

The term hysteroscopy is used to determine the procedure during which an endoscopic view of the endometrial cavity is achieved with the help of a type of endoscopic device called “the hysteroscope.” Hysteroscopy is used to assist the diagnosis for a series of female pathology. Apart from its diagnostic value, hysteroscopy can also be used for operative procedures including ablation and resection. Both diagnostic and operative hysteroscopy have been used for a number of years and various studies have been published to describe their success and complication rates throughout this period. Diagnostic hysteroscopy is relatively safe, whereas complications occur more frequently when operative hysteroscopy is used. These complications include uterine perforation, hemorrhage, fluid overload, gas embolization, and hyponatremia. The rate in the appearance of these complications is dependent on the type of the hysteroscopic procedure, the distending medium, and the experience of the hysteroscopist. To avoid any problems concerning the application of hysteroscopic procedures, it is important to take the necessary precautions both preoperatively and intraoperatively. For example, the preoperative use of thinning agents of the endometrium and the reduction of the operating time, or the avoidance of cutting too deeply into the myometrium, are some of the parameters to be considered when hysteroscopy is in argument. [ABSTRACT FROM AUTHOR]

Abstract: Several chemotherapy and hormonal therapy regimens have been used in advanced endometrial cancer. In this review we have systematically evaluated the available data from randomized trials on survival. We searched MEDLINE, EMBASE and the Cochrane Library (last search April 2005) for randomized controlled trials evaluating various chemotherapy or hormonal therapy regimens in locally advanced or metastatic endometrial cancer. We focused on survival outcomes and examined trial characteristics pertaining to quality and potential biases. Across 17 eligible trials (2964 patients randomized), only 4 regimens were involved in more than one trial, and only two trials had used the same comparison of regimens. A statistically significant effect in survival was seen only in one recent trial, but it was borderline (P =0.032) and amounted to only 3 months difference in median survival. Three more trials reported some survival benefits, but these were seen only after specific adjustments, and the difference was against the experimental arm in one of these three trials. Only four trials (24%) apparently analyzed all randomized patients and none of the trials were blinded. Median survival was seemingly longer in more recent compared with older trials, but this effect was driven by the inclusion of significantly fewer patients with poor performance status in more recent trials (P <0.001). Overall, randomized evidence on systemic treatment in advanced endometrial cancer is fragmented and survival benefits for specific regimens are questionable. [Copyright &y& Elsevier]

STUDY QUESTION Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? SUMMARY ANSWER Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. WHAT IS KNOWN ALREADY Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). MAIN RESULTS AND THE ROLE OF CHANCE Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] –2.4 [95% CI –4.1 to –0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM –1.8 [95% CI –3.1 to –0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM –1.5 [95% CI –2.6.1 to –0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM –0.07 [95% CI –0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM –0.07 [95% CI –0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8–38.1%] and a 35% [95% CI 26.6–43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. LIMITATIONS, REASONS FOR CAUTION The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. WIDER IMPLICATIONS OF THE FINDINGS In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V. F.M. and I.R. declared no conflicts of interest. TRIAL REGISTRATION NUMBER The study was registered at Clinical Trials Gov. (NCT04108039). [ABSTRACT FROM AUTHOR]

A meta-analysis of four trials showed significant advantage in pregnancy and delivery rates with aromatase inhibitors compared with CC in women with PCOS. A recent randomized trial demonstrated no clear benefit. [Copyright &y& Elsevier]

Genital Chlamydia trachomatis infection is the principal cause of bacterial sexually transmitted disease in industrialized countries. A wide spectrum of pathologic conditions has been associated with the disease ranging from urethritis, cervicitis, to pelvic inflammatory disease, ectopic pregnancy, tubal infertility and cervical neoplasia.Screening for genital Chlamydia infection may prevent its serious complications. The need of a comprehensive European screening policy has been recently underlined by PACMeR's scientific committee. Anyhow invitational screening programs are only at the beginning. Chlamydia trachomatis control ‘‘orphan’’ and women's health at risk.Until organized programs are developed, implementation of opportunistic screening is mandatory. Since the infection is more commonly observed among juvenile females proper testing of the young women is recommended. As asymptomatic young women in reproductive age are more eager to visit gynaecologists for periodical gynaecological examination and councelling (cervical cytology, breast examination, contraception and family planning), gynaecologist represents the only specialist able to provide early diagnosis of Chlamydia trachomatis.Gynaecologists are called to play a new role in public healthcare, being ‘‘gatekeepers’’ for the early detection of the disease, emphasizing their crucial part in young women's health. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between the number of oocytes retrieved and cumulative live birth rates.Design: Retrospective multicenter analysis using individual patient data.Setting: Tertiary referral hospitals.Patient(s): In total, 14,469 patients were analyzed. The study included the first cycle of patients stimulated for IVF/intracytoplasmic sperm injection (ICSI) from 2009 to 2014. All patients included in the analysis had either delivered a baby or had used all their embryos after their first stimulated cycle. All patients had vitrification as cryopreservation method. All women were followed up for at least 2 years.Intervention(s): Ovarian stimulation with GnRH antagonist protocol for IVF/ICSI.Main Outcome Measure(s): The primary outcome was the cumulative live birth rate defined as the delivery of at least one live-born infant (>24 weeks of gestation) in the fresh or in the subsequent frozen-thawed cycles in relation to the number of oocytes retrieved. Only the first delivery was considered in the analysis. The secondary outcome was live birth after the fresh IVF/ICSI cycle only.Result(s): Cumulative live birth rates steadily increased with the number of oocytes, reaching 70% when ≥25 oocytes were retrieved. Interestingly, no plateau in cumulative live birth rates was observed, but a moderate increase of 5.1% on average was detected beyond 27 oocytes. Regarding the fresh cycle outcome, live birth probability increased up to seven oocytes retrieved and remained relatively unchanged (increase or decrease of ≤5%) between seven and 20 oocytes retrieved. However, a drop in fresh live birth rates was identified thereafter, which could be attributed to the progressive increase in "freeze-all" cycle rate with the number of oocytes retrieved, exceeding 20% in patients with >20 oocytes retrieved.Conclusion(s): This is the largest multicenter study evaluating for the first time the impact of ovarian response on cumulative live birth rate. The significant progressive increase of cumulative live birth rate with the number of oocytes in our study suggests that ovarian stimulation may not have a detrimental effect on oocyte/embryo quality in good-prognosis women less than 40 year old. Nevertheless, although very high ovarian response may further increase cumulative live birth rates, ovarian stimulation should be rational and avoid extreme response in terms of oocytes retrieved to preserve patients' convenience and safety and avoid ovarian hyperstimulation syndrome or other iatrogenic complications. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does the diagnosis of mosaicism affect ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A)? SUMMARY ANSWER Our analysis of 36 395 blastocyst biopsies across eight genetic testing laboratories revealed that euploidy rates were significantly higher in providers reporting low rates of mosaicism. WHAT IS KNOWN ALREADY Diagnoses consistent with chromosomal mosaicism have emerged as a third category of possible embryo ploidy outcomes following PGT-A. However, in the era of mosaicism, embryo selection has become increasingly complex. Biological, technical, analytical, and clinical complexities in interpreting such results have led to substantial variability in mosaicism rates across PGT-A providers and clinics. Critically, it remains unknown whether these differences impact the number of euploid embryos available for transfer. Ultimately, this may significantly affect clinical outcomes, with important implications for PGT-A patients. STUDY DESIGN, SIZE, DURATION In this international, multicenter cohort study, we reviewed 36 395 consecutive PGT-A results, obtained from 10 035 patients across 11 867 treatment cycles, conducted between October 2015 and October 2021. A total of 17 IVF centers, across eight PGT-A providers, five countries and three continents participated in the study. All blastocysts were tested using trophectoderm biopsy and next-generation sequencing. Both autologous and donation cycles were assessed. Cycles using preimplantation genetic testing for structural rearrangements were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS The PGT-A providers were randomly categorized (A to H). Providers B, C, D, E, F, G, and H all reported mosaicism, whereas Provider A reported embryos as either euploid or aneuploid. Ploidy rates were analyzed using multilevel mixed linear regression. Analyses were adjusted for maternal age, paternal age, oocyte source, number of embryos biopsied, day of biopsy, and PGT-A provider, as appropriate. We compared associations between genetic testing providers and PGT-A outcomes, including the number of chromosomally normal (euploid) embryos determined to be suitable for transfer. MAIN RESULTS AND THE ROLE OF CHANCE The mean maternal age (±SD) across all providers was 36.2 (±5.2). Our findings reveal a strong association between PGT-A provider and the diagnosis of euploidy and mosaicism. Amongst the seven providers that reported mosaicism, the rates varied from 3.1% to 25.0%. After adjusting for confounders, we observed a significant difference in the likelihood of diagnosing mosaicism across providers (P  < 0.001), ranging from 6.5% (95% CI: 5.2–7.4%) for Provider B to 35.6% (95% CI: 32.6–38.7%) for Provider E. Notably, adjusted euploidy rates were highest for providers that reported the lowest rates of mosaicism (Provider B: euploidy, 55.7% (95% CI: 54.1–57.4%), mosaicism, 6.5% (95% CI: 5.2–7.4%); Provider H: euploidy, 44.5% (95% CI: 43.6–45.4%), mosaicism, 9.9% (95% CI: 9.2–10.6%)); and Provider D: euploidy, 43.8% (95% CI: 39.2–48.4%), mosaicism, 11.0% (95% CI: 7.5–14.5%)). Moreover, the overall chance of having at least one euploid blastocyst available for transfer was significantly higher when mosaicism was not reported, when we compared Provider A to all other providers (OR = 1.30, 95% CI: 1.13–1.50). Differences in diagnosing and interpreting mosaic results across PGT-A laboratories raise further concerns regarding the accuracy and relevance of mosaicism predictions. While we confirmed equivalent clinical outcomes following the transfer of mosaic and euploid blastocysts, we found that a significant proportion of mosaic embryos are not used for IVF treatment. LIMITATIONS, REASONS FOR CAUTION Due to the retrospective nature of the study, associations can be ascertained, however, causality cannot be established. Certain parameters such as blastocyst grade were not available in the dataset. Furthermore, certain platform-related and clinic-specific factors may not be readily quantifiable or explicitly captured in our dataset. As such, a full elucidation of all potential confounders accounting for variability may not be possible. WIDER IMPLICATIONS OF THE FINDINGS Our findings highlight the strong need for standardization and quality assurance in the industry. The decision not to transfer mosaic embryos may ultimately reduce the chance of success of a PGT-A cycle by limiting the pool of available embryos. Until we can be certain that mosaic diagnoses accurately reflect biological variability, reporting mosaicism warrants utmost caution. A prudent approach is imperative, as it may determine the difference between success or failure for some patients. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Torres Quevedo Grant, awarded to M.P. (PTQ2019-010494) by the Spanish State Research Agency, Ministry of Science and Innovation, Spain. M.P. L.B. A.R.L. A.L.R.d.C.L. N.P.P. M.P. D.S. F.A. A.P. B.M. L.D. F.V.M. D.S. M.R. E.P.d.l.B. A.R. and R.V. have no competing interests to declare. B.L. R.M. and J.A.O. are full time employees of IB Biotech, the genetics company of the Instituto Bernabeu group, which performs preimplantation genetic testing. M.G. is a full time employee of Novagen, the genetics company of Cegyr, which performs preimplantation genetic testing. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Ovarian stimulation for assisted reproductive technology is traditionally started in the early follicular phase. The essential rationale is to allow timely follicle growth and oocyte retrieval to ensure synchronization of the in-vitro cultured embryos with the receptive period of the endometrium in a fresh transfer cycle. In addition, conventional thought suggested that follicle recruitment happened only once, around menstruation. A deeper understanding of folliculogenesis, advances in cryobiology and an increasing proportion of freeze-all cycles provide a unique opportunity here. Experience from oncofertility patients as well as infertile women and oocyte donors who underwent ovarian stimulation in different phases of the menstrual cycle, dubbed 'random start' cycles, suggests that the number of oocytes collected and their reproductive potential do not depend on the time of starting ovarian stimulation, although the duration of stimulation and gonadotrophin consumption can vary slightly. It may be time to free both patients and clinics from the obsession with starting ovarian stimulation in the early follicular phase in planned freeze-all cycles. The flexibility provided by random start cycles is one aspect of individualizing treatment to patients' needs. [ABSTRACT FROM AUTHOR]

(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p < 0.001). The presence of adenomyosis significantly decreased the clinical pregnancy rates (aOR 0.62, 95% CI: 0.39–0.98, p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27–0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98–4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

To evaluate whether patients with high-serum progesterone levels before frozen embryo transfer (FET) under hormonal replacement therapy present with worse reproductive outcomes. A cohort retrospective study. A university-affiliated fertility center. A total of 3,183 FET cycles in patients receiving hormonal replacement therapy between March 2009 and December 2020 were included. The luteal phase was covered with 200 mg per 8 hours of vaginal micronized progesterone either alone or in combination with a daily subcutaneous injection of 25 mg of progesterone. A total of 1,360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1,024 were euploid ET (eu-FET) after preimplantation genetic testing for aneuploidies, and 799 cycles were frozen heterologous ET (het-FET). All patients had adequate serum progesterone levels (≥10.6 ng/mL) before the procedure. Frozen embryo transfer cycles. Clinical pregnancy, miscarriage, and live birth rates (LBRs). Median (P25; P75) serum progesterone level before FET was 14.39 (12.43–17.49) ng/mL. Progesterone levels were significantly higher in the group under vaginal plus subcutaneous progesterone (15.96 [13.74–21.60] vs. 14.09 [12.19–16.95]). No differences in clinical pregnancy, miscarriage, and LBR were observed based on the use of vaginal or vaginal plus subcutaneous progesterone for each of the groups (hom-FET, eu-FET, and het-FET). Live birth rates were comparable among patients in the highest centile of serum progesterone levels (≥p90) (22.33 ng/mL) and the rest of the patients (p<90) (43.9% vs. 41.3%). Patients with progesterone levels ≥p90 presented lower body mass index than those in the lower centiles (

Recurrent miscarriage is the loss of two or more consecutive pregnancies and affects 1% of couples trying to conceive. It has proven to be frustrating for both patient and clinician. The majority of investigations and treatments offered remain controversial. However, practice must be evidence based and unproven investigations and treatments should be abandoned. Psychological support is of paramount importance since a significant number of women attending RM clinics have high levels of anxiety or are clinically depressed. Setting up a RM clinic is important to provide a dedicated service to couples with RM so as to avoid unnecessary and potentially harmful treatments, and also to recruit patients in trials that will delineate causes and efficacy of treatments. [ABSTRACT FROM AUTHOR]

• c.919A>G genotypes AG/GG are associated with higher CPR versus genotype AA • c.919A>G genotypes AG/GG are associated with higher LBR versus genotype AA • c.2039A>G genotype GG is associated with lower CLBR versus genotype AA Is there an association between FSHR sequence variants and reproductive outcomes following IVF in predicted normoresponders? Multicentre prospective cohort study conducted from November 2016 to June 2019 in Vietnam, Belgium and Spain including patients aged <38 years, and undergoing IVF with a predicted normal response with fixed-dose 150 IU rFSH in an antagonist protocol. Genotyping was performed for three FSHR (c.919A>G, c.2039A>G, c.-29G>A) and one FSHB sequence variants (c.-211G>T). Clinical pregnancy rate (CPR), live birth rate (LBR) and miscarriage rate in the first embryo transfer and cumulative live birth rate (CLBR) were compared between the different genotypes. A total of 351 patients underwent at least one embryo transfer. Genetic model analysis that adjusted for patient age, body mass index, ethnicity, type of embryo transfer, embryo stage and number of top-quality embryos transferred revealed a higher CPR for homozygous patients for the variant allele G of c.919A>G when compared to patients with genotype AA (60.3% versus 46.3%, adjusted odds ratio [ORadj] 1.96, 95% confidence interval [CI] 1.09–3.53). Also, c.919A>G genotypes AG and GG presented a higher CPR and LBR when compared with genotype AA (59.1% versus 46.3%, ORadj 1.80, 95% CI 1.08–3.00, and 51.3% versus 39.0%, ORadj 1.69, 95% CI 1.01–2.80, respectively). Cox regression models revealed a statistically significantly lower CLBR for c.2039A>G genotype GG in the codominant model (hazard ratio [HR] 0.66, 95% CI 0.43–0.99). These results demonstrate a previously unreported association between variant c.919A>G genotype GG and higher CPR and LBR in infertile patients and reinforce a potential role for genetic background in predicting the reproductive prognosis following IVF. [ABSTRACT FROM AUTHOR]

Objective: To assess endocrine differences during early luteal phase according to mode of triggering final oocyte maturation with or without luteal phase support (LPS). Design: A prospective randomized study. Setting: University center for reproductive medicine. Patient(s): Four oocyte donors each underwent four consecutive cycles. Intervention(s): To avoid interpatient variation, each donor underwent the same stimulation regimen. However, different modes of triggering final oocyte maturation and LPS were administered: A) 10,000 IU hCG and standard LPS; B) GnRH agonist (GnRHa; 0.2 mg triptorelin), and 35 hours later 1,500 IU hCG, and standard LPS; C) GnRH agonist (0.2 mg triptorelin) and standard LPS; and D) GnRH agonist (0.2 mg triptorelin) without LPS. Main Outcome Measure(s): Blood sampling was performed on the day of ovulation trigger, ovulation trigger + 1 day, and ovum pick-up + 5 days. Serum E2, FSH, LH, and P were measured. Result(s): The early luteal phase steroid levels following GnRHa trigger and modified luteal phase support (B) were similar to those seen after hCG trigger (A). However, significant differences were seen between groups A and B compared with C and D, as well as between groups C and D. Conclusion(s): Administration of a single bolus of GnRHa effectively induced LH and FSH surges in oocyte donors stimulated with recombinant FSH and cotreated with a GnRH antagonist. However, gonadotropin and steroid levels differed significantly according to the type of luteal phase support used after GnRHa trigger. European Community Clinical Trial System (EudraCT) Number: 2009-009429-26. [ABSTRACT FROM AUTHOR]

The author discusses importance of meta-analyses of drugs and treatment techniques. He mentions simple insight into the deviation from the initial concept of meta analysis by scrutinizing PubMed. The author discusses the impact of increased number of meta analysis like decreases in the quality and value of systemic reviews. He also discusses the role of medical editors and reviewers, scientific evidence and stepping toward high-quality medical research.

Study Question: Does ovarian stimulation affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) following IVF treatment.Summary Answer: Despite no significant differences in the risks of PTB and LBW between stimulated and unstimulated IVF in the present study, the study cannot exclude the effect of ovarian stimulation on the perinatal outcomes following IVF.What Is Already Known: Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared to spontaneously conceived pregnancies attributed to the underlying infertility and the in vitro fertilization techniques. It is of interest to determine the effect size of ovarian stimulation use in achieving a live birth and whether ovarian stimulation that is routinely used in IVF, affects perinatal outcomes of birth weight and gestational age at delivery compared to unstimulated IVF.Study Design, Size, Duration: Anonymous data were obtained from the Human Fertilisation and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1991 to 2011 comprising a total of 591 003 fresh IVF ± ICSI cycles involving 584 835 stimulated IVF cycles and 6168 unstimulated IVF cycles were analyzed.Participants/materials, Setting, Methods: Data on all women undergoing either stimulated or unstimulated fresh IVF ± ICSI cycles during the period from 1991 to 2011 were analyzed to compare live birth rates, singleton live birth rates, perinatal outcomes of PTB, early PTB (<32 weeks), LBW and very LBW (<1500 grams) among singleton live births. Adjusted logistic regression was performed for each perinatal outcome for confounding factors: female age, period of treatment, cause of infertility, number of previous IVF cycles and previous live birth.Main Results and the Role Of Chance: Analysis of the large nationwide data demonstrated 3.5 times (95% confidence interval (CI): 3.1-3.9) as many unstimulated IVF cycles being required to achieve one live birth compared to stimulated IVF and 2.9 times (95% CI: 2.6-3.2) as many unstimulated IVF cycles being required to achieve one singleton live birth compared to stimulated IVF. There was no significant difference in the unadjusted odds for PTB (odds ratio (OR) 1.27, 95% CI: 0.80-2.00) and LBW (OR 1.48, 95% CI: 0.90-2.42) between stimulated and unstimulated IVF cycles. There was no significant difference in the risk of the adverse perinatal outcomes after adjusting for potential confounders; PTB (adjusted odds ratio (aOR) 1.43, 95% CI: 0.91-2.26) and LBW (aOR 1.58, 95% CI: 0.96-2.58).Limitations, Reasons For Caution: Although the analysis was adjusted for a number of important confounders, the dataset had no information on smoking, body mass index (BMI) and the medical history of women during pregnancy to allow adjustment. Anonymized nature of the dataset did not make it permissible to analyse one cycle per woman. Given the smaller number of perinatal events with unstimulated IVF, a larger study is needed to investigate further.Wider Implications Of the Findings: Analysis of this large dataset demonstrates that ovarian stimulation has a vital role in maximizing efficacy of IVF. Although there were no significant differences for PTB and LBW following stimulated compared to unstimulated IVF, the CIs were wide enough to include possible clinically important effects.Study Funding/competing Interests: No funding was obtained. There are no competing interests to declare. [ABSTRACT FROM AUTHOR]

Study Question: Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation?Summary Answer: The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS.What Is Known Already: Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF.Study Design, Size, Duration: This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample.Participants/materials, Setting, Methods: Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 μg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy).Main Results and the Role Of Chance: FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)).Limitations, Reasons For Caution: The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age.Wider Implications Of the Findings: The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase.Study Funding/competing Interest(s): This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests.Trial Registration Number: The study was registered at Clinical Trials Gov (NCT03555942). [ABSTRACT FROM AUTHOR]

Cycle monitoring via ultrasound and serum-based hormonal assays during medically assisted reproduction (MAR) can provide information on ovarian response and assist in optimizing treatment strategies in addition to reducing complications such as ovarian hyperstimulation syndrome (OHSS). Two surveys conducted in 2019 and 2020, including overall 24 fertility specialists from Europe, Asia and Latin America, confirmed that the majority of fertility practitioners routinely conduct hormone monitoring during MAR. However, blood tests may cause inconvenience to patients. The reported drawbacks of blood tests identified by the survey included the validity of results from different service providers, long waiting times and discomfort to patients due to travelling to clinics for tests and repeated venepunctures. Historically, urine-based assays were used by fertility specialists in clinics but were subsequently replaced by more practical and automated serum-based assays. A remote urine-based hormonal assay could be an alternative to current serum-based testing at clinics, reducing the inconvenience of blood tests and the frequency of appointments, waiting times and patient burden. Here we provide an overview of the current standard of care for cycle monitoring and review the literature to assess the correlation between urine-based hormonal assays and serum-based hormonal assays during MAR. In addition, in this review, we discuss the evidence supporting the introduction of remote urine-based hormonal monitoring as part of a novel digital health solution that includes remote ultrasound and tele-counselling to link clinics and patients at home. [ABSTRACT FROM AUTHOR]

• Comparing embryos, more males than females develop to the blastocyst stage. • Male blastocysts exhibit a higher aneuploidy rate. • The live birth rate is similar between male and female single blastocyst transfers. Is there any imbalance in the sex ratio at the blastocyst stage of human embryos? And what is the sex ratio in euploid, transferred, implanted blastocysts and at birth? Embryos from 646 women undergoing 921 preimplantation genetic testing for aneuploidy (PGT-A) cycles from September 2017 to February 2020 were included. Data from the chromosomal constitution of 2637 biopsied blastocysts were retrospectively analysed. Trophectoderm samples were analysed by next-generation sequencing. Embryos were categorized as euploid, mosaic or aneuploid. A total of 548 blastocysts diagnosed as euploid were warmed and transferred in a subsequent single-embryo transfer cycle. The blastocyst sex ratio was skewed in favour of male sex with 53.1% (1401/2637) of blastocysts diagnosed as male and 46.9% (1236/2637) as female (sex ratio 1.13, 95% confidence interval [CI] 1.05–1.22). Following biopsy and PGT-A, 41.2% (1086/2637) of blastocysts were classified as euploid, 7.7% (202/2637) as mosaic and 51.2% (1349/2637) as aneuploid. More chromosome euploidy was observed among female than male blastocysts (adjusted odds ratio 1.29, 95% CI 1.08–1.55) after adjusting for female age, male age and gonadotrophin dose. Euploid blastocysts were comparable between the sexes (sex ratio 0.99, 95% CI 0.88–1.11). No significant differences were observed between the sexes in implantation (sex ratio 0.86, 95% CI 0.68–1.08), miscarriage (sex ratio 1, 95% CI 0.51–1.97) or live birth rate (sex ratio 0.85, 95% CI 0.66–1.08). More male than female embryos develop to the blastocyst stage. Male blastocysts exhibit a higher aneuploidy rate. The capacity to implant and lead to a live birth is similar between the sexes. [ABSTRACT FROM AUTHOR]

Objective: To assess the definitions for “poor ovarian responders” used among randomized trials for the treatment of women with impaired response to stimulation. Design: Systematic review. Setting: None. Patient(s): Poor ovarian responders. Intervention(s): Treatment modalities for the management of poor ovarian responders. Main Outcome Measure(s): Number and nature of the criteria used to define poor ovarian response to stimulation and threshold values used. Result(s): Among 47 randomized trials, 41 different definitions for the patients with poor ovarian response have been used. No more than 3 trials used the same definition, whereas even trials from the same research groups used different definitions across different trials. None of the criteria used was adopted in more than 50% of the trials. Age and antral follicle count were adopted only in 9% of the definitions, whereas the criteria of number of follicles on the final stimulation day and number of oocytes retrieved were used in more than 40% of the trials; nonetheless, even for these criteria, the threshold values were consistently different. Conclusion(s): The variability regarding the definition of poor ovarian responders appears to be striking. Although the Bologna criteria developed by European Society for Human Reproduction and Embryology consensus in 2011 aim to define a consistent group of patients, their applicability needs to be tested through clinical trials. Meanwhile, meta-analyses of the currently available trials should be strongly discouraged because they may lead to the adoption of interventions of ambiguous value. [ABSTRACT FROM AUTHOR]