Search

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]

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]

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]

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]

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]

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]

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 (

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]

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]

Objective: To assess whether there is an increased risk of infertility in women that have previously undergone ovarian stimulation and oocyte retrieval for oocyte donation. Design: Cross-sectional survey. Setting: Tertiary referral center. Patient(s): A total of 194 past oocyte donors. Intervention(s): Telephone questionnaire. Main Outcome Measure(s): Incidence of infertility after oocyte donation. Result(s): Of the women who indicated having pursued conception after oocyte donation, 95% (57/60) became pregnant unassisted. Before oocyte donation, 41 women in this cohort had already been trying to conceive, of which 38 had delivered a child and 3 (7.3%) had needed infertility treatment. Conclusion(s): The data suggest that oocyte donation does not affect short-term reproductive health. [ABSTRACT FROM AUTHOR]

Objective: To evaluate if increasing the interval between a failed fresh embryo transfer and a subsequent frozen embryo transfer (FET) cycle has any effect on clinical pregnancy rates (CPRs).Design: Retrospective cohort study.Setting: University-based tertiary referral center.Patient(s): Women who underwent at least one FET after ovarian stimulation for in vitro fertilization (IVF) and a failed fresh embryo transfer attempt from January 2010 to November 2014. We divided our sample according to the "timing" of the first FET (TF-FET), defined by the interval between oocyte retrieval and the FET cycle start date. The start of the FET was classified as either immediate (≤22 days after oocyte retrieval) or delayed (>22 days after oocyte retrieval).Intervention(s): None.Main Outcome Measure(s): CPR after the first FET.Result(s): A total of 1,183 FET cycles (performed in 1,087 women) were included in our study. No significant differences were found between the immediate and delayed FET groups regarding age, number of oocytes retrieved, number of good-quality embryos produced, embryo developmental stage at FET, and number of frozen embryos transferred. Most importantly, the CPRs of the first FET did not differ significantly according to the TF-FET (32.5% after immediate FET vs. 31.7% after delayed FET), even after adjusting for potential confounding with the use of multivariable logistic regression.Conclusion(s): FETs performed immediately after fresh IVF cycles had CPRs similar to those postponed to a later time. Therefore, deferring FETs may unnecessarily prolong time to pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To compare clinical outcomes of fresh embryo transfer (ET) and vitrified-warmed ET in an artificial endometrial priming cycle in patients with polycystic ovaries (PCO) or polycystic ovary syndrome (PCOS) who underwent oocyte in vitro maturation (IVM) in non–hCG-primed cycles. Design: Prospective cohort study. Setting: University-based tertiary referral center. Patient(s): Thirty-nine consecutive patients <37 years old with PCO or PCOS, who underwent 73 cycles of immature oocyte retrieval. Intervention(s): Immature oocyte collection after ovarian stimulation with a cumulative dose of 450 IU uFSH or highly purified hMG, but without hCG priming. IVM of oocytes followed by ET if endometrium thickness ≥6 mm. Embryo vitrification at the cleavage stage. ET in an artificial cycle. Main Outcome Measure(s): Implantation rate (IR) and clinical pregnancy rate (CPR). Result(s): Fresh ET after IVM resulted in an IR of 6.9% (5/72) per ET and a CPR of 9.4% (5/53). ET of vitrified-warmed IVM embryos in an artificial cycle resulted in significantly better outcomes (IR 21.9% [7/32] and CPR 31.8% [7/22] per ET). Conclusion(s): A non–hCG-primed IVM system in PCO or PCOS performs poorly when embryos are transfered in a fresh cycle. Transfer of vitrified-warmed IVM embryos in an artificial cycle leads to significantly improved clinical outcomes. These data illustrate that IVM embryos in PCO or PCOS have good survival rates and suggest that hCG may be needed to support endometrial receptivity in the fresh IVM cycle. [ABSTRACT FROM AUTHOR]