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

Purpose: To compare fertility outcomes of obese patients (body mass index [BMI] ≥ 30 kg/m 2 ) undergoing superovulation and intrauterine insemination (SO-IUI) using gonadotropins versus letrozole., Methods: A single centre retrospective cohort study of obese patients undergoing SO-IUI using gonadotropins or letrozole between January/2019 and June/2022. Primary outcome was clinical pregnancy rate (intrauterine pregnancy with positive fetal heart rate). Secondary outcomes included rates of multifollicular development, multiple pregnancy, spontaneous abortion and cycle cancellation. Subgroup analysis was done stratifying by obesity class. A multivariate logistic regression model was used for primary/secondary outcomes, adjusting for clinically determined covariates., Results: Out of 802 total identified SO-IUI cycles, 715 cycles were completed (518-gonadotropins and 197-letrozole cycles). The clinical pregnancy rates were not significantly different in obese patients undergoing SO-IUI with gonadotropins versus letrozole when adjusted for age, gravidity, parity, cause of infertility, IUI cycle number, endometrial thickness, sperm source and post-wash motile sperm count (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 0.72-2.59). Similarly, no significant associations were found in spontaneous abortion (aOR1.46, 95%CI 0.42-5.08), multiple pregnancy (aOR1.33, 95%CI 0.20-8.88) or cancellation rates (OR0.89, 95%CI 0.55-1.45) between the two groups. The rates of multifollicular development were also comparable between the two groups (aOR0.51, 95% CI 0.19-1.38). For cycles involving gonadotropins, higher BMI classes required higher total gonadotropin dose (p < 0.001)., Conclusion: After adjusting for patient and cycle factors, gonadotropins and letrozole led to comparable odds of achieving pregnancy in obese patients undergoing SO-IUI. Future research in the obese population will help to better understand how to optimize fertility treatments for this growing population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: This study aimed to evaluate the effectiveness of a clinical decision support tool, Opt-IVF, in achieving the following outcomes: reducing the total cumulative dosage of Gonadotropins (Gns) used during controlled ovarian stimulation cycles and reducing the repeated ultrasonograms (USG) for monitoring follicular growth without compromising the number of good quality blastocysts obtained. The study design employed a multi-center randomized trial. The study enrolled 115 women aged 25-45 years undergoing IVF. Among the participants, 55 were randomly assigned to the intervention group (Opt-IVF), and 60 were randomly assigned to the control group. The intervention involved using a clinical decision support tool, Opt-IVF, to guide Gn dosing and trigger dates. The participants in the intervention group required significantly lower cumulative Gn dosage. The intervention group had higher numbers of oocytes retrieved and M2 retrieved than the control group. The number of good-quality blastocysts, the good-quality blastocyst rate, the ovarian sensitivity index (OSI), and the pregnancy rate in the intervention group were significantly higher than in the control group. The utilization of the clinical decision support tool led to several positive outcomes, including eliminating the need for ultrasound exams after day 5, reducing the dosage of Gn required, and yielding significantly higher numbers of high-quality blastocysts and higher pregnancy rates. Thus, Opt-IVF can successfully provide a personalized, optimized, and simplified approach to superovulation. Opt-IVF consistently outperformed the clinical teams in most of the outcomes. Clinical trials registration: ClinicalTrials.gov (ID - NCT05811065). Date of Registration: 15 March 2023. Date of enrollment of the first subject: 20 March 2023., Lay Summary: The high cost of IVF is a result of costly drugs, fixed prices for infrastructure, extensive testing required, and labor costs for physicians and other healthcare personnel. Superovulation, which involves the drug-induced release of multiple eggs needed for IVF, accounts for a significant share of these costs. Current approaches to superovulation involve almost daily monitoring of follicle development using ultrasound and/or blood tests. The daily dosage of stimulatory hormones is then prescribed by physicians based on empirical data and clinical experience. However, the dose is not optimized for each patient, and overstimulation complications can occur. The cost of testing and drugs makes this stage very expensive. To overcome the shortcomings of this system, we have developed a decision support tool (Opt-IVF) that can provide a personalized model-optimized dosage profile for each patient. The clinical results show that Opt-IVF optimizes and personalizes dosage, reduces testing, and provides better outcomes for patients.

Background: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes., Methods: This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses., Setting: Single reproductive medical center., Subjects: All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included., Exposure: Next-generation sequencing platforms for chromosomal analysis., Main Outcome Measures: Blastocyst formation and euploid blastocyst rates., Results: In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy., Conclusion: In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS)., Methods: Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS)., Results: Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome., Conclusion: Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Objective: To compare two cancellation policies in controlled ovarian stimulation-intrauterine insemination (COS-IUI) cycles to lower the risk of multiple pregnancies (MP)., Design: We performed a bicentric retrospective cohort study in two academic medical centers: Angers (group A) and Besançon (group B) University Hospitals. We included 7056 COS-IUI cycles between 2011 and 2019. In group A, cancellation strategy was based on an algorithm taking into account the woman's age, the serum estradiol level, and the number of follicles of 14 mm or greater on ovulation trigger day. In group B, cancellation strategy was case-by-case and physician-dependent, based on the woman's age, number of follicles of 15 mm or greater, and the previous number of failed COS-IUI cycles, without any predefined cut-off. Our main outcome measures were the MP rate (MPR) and the live-birth rate (LBR)., Results: We included 884 clinical pregnancies (790 singletons, 86 twins, and 8 triplets) obtained from 6582 COS-IUI cycles. MPR was significantly lower in group A compared with group B (8.1% vs 13.3%, P = 0.01), but LBR were comparable (10.8% vs 11.8%, P = 0.19). Multivariate logistic regression found the following to be risk factors for MP: the "cancellation strategy" effect (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.02-2.60) and the number of follicles of 14 mm or greater (aOR 1.39, 95% CI 1.16-1.66). Cycle cancellation rate for excessive response was significantly lower in group A compared with group B (1.3% vs 2.4%, P < 0.001)., Conclusions: The use of an algorithm based on the woman's age, serum estradiol level and number of follicles of at least 14 mm on trigger day allows the MPR to be reduced without impacting the LBR., (© 2024 International Federation of Gynecology and Obstetrics.)

Objectives: To investigate treatment approaches for fertility preservation patients, with a focus on timing of oocyte retrieval, and to determine whether their characteristics differ from those of other IVF patients. Additionally, to evaluate the significance of follicle size on triggering day in the context of fertility preservation., Methods: This retrospective cohort study was conducted in a tertiary, university-affiliated medical center. It compared 140 matched patients undergoing social fertility preservation to 140 patients undergoing IVF treatment due to male factor infertility., Results: Patients undergoing fertility preservation received a higher initial gonadotropin dose and had more oocytes retrieved than the control group. Within the fertility preservation cohort, a negative correlation was observed between the rate of large follicles and the number of retrieved oocytes. While there was no significant association between rate of large follicles and oocyte maturation rate in the entire group, age-stratified analysis revealed a negative relationship. Analysis revealed that although traditional treatment determinants such as follicular size and gonadotropin dosing were considered, peak estradiol levels were consistently identified as significant predictors of treatment outcomes., Conclusions: Physicians may modify treatments for fertility preservation, emphasizing a higher gonadotropin dosage to maximize oocyte retrieval. Elevated estradiol levels can serve as a real-time predictive marker for the number of mature oocytes. While treatment strategies can influence outcomes, intrinsic patient factors, particularly baseline ovarian function, remain crucial. These results challenge beliefs regarding the importance of larger follicles and suggest the need for a tailored approach, considering patient age and specific fertility preservation objectives., (© 2024. The Author(s).)

Objective: Ovarian stimulation (OS) with high daily gonadotropin doses are commonly offered to patients attempting social/elective egg freezing. However, the optimal daily gonadotropin dose that would allow a higher oocyte yield in the successive IVF cycle attempt was not settled and should be determined., Patients and Methods: Data from all women admitted to our IVF unit for social/EEF, who underwent two consecutive IVF cycle attempts, with only those who used in the first attempt a starting daily gonadotropin dose of 300IU were analyzed. Patients characteristics and OS variables were used in an attempt to build a logistic model, helping in determining the daily gonadotropin dose that should be offered to patient during their second EEF attempt, aiming to further increase their oocyte yield., Results: Three hundred and thirteen consecutive women undergoing two successive IVF cycle attempts were evaluated. Using logistic regression model, two equations were developed using individual patient-level data that determine the daily gonadotropin dose needed aiming to increase the oocyte yield in the successive cycle. (a): X=-0.514 + 2.87*A1 + 1.733*A2-0.194* (E2/1000) and (b): P = EXP(X) / [1 + EXP(X)]., Conclusions: Using the aforementioned equations succeeded in determining the daily gonadotropin dose that might result in increasing oocyte yield, with an AUC of 0.85. Any additional oocyte retrieved to these EEF patients might get them closer to fulfil their desire to parenthood., (© 2024. The Author(s).)

Purpose: Ovarian stimulation with gonadotropins is crucial for obtaining mature oocytes for in vitro fertilization (IVF). Determining the optimal gonadotropin dosage is essential for maximizing its effectiveness. Our study aimed to develop a machine learning (ML) model to predict oocyte counts in IVF patients and retrospectively analyze whether higher gonadotropin doses improve ovarian stimulation outcomes., Methods: We analyzed the data from 9598 ovarian stimulations. An ML model was employed to predict the number of mature metaphase II (MII) oocytes based on clinical parameters. These predictions were compared with the actual counts of retrieved MII oocytes at different gonadotropin dosages., Results: The ML model provided precise predictions of MII counts, with the AMH and AFC being the most important, and the previous stimulation outcome and age, the less important features for the prediction. Our findings revealed that increasing gonadotropin dosage did not result in a higher number of retrieved MII oocytes. Specifically, for patients predicted to produce 4-8 MII oocytes, a decline in oocyte count was observed as gonadotropin dosage increased. Patients with low (1-3) and high (9-12) MII predictions achieved the best results when administered a daily dose of 225 IU; lower and higher doses proved to be less effective., Conclusions: Our study suggests that high gonadotropin doses do not enhance MII oocyte retrieval. Our ML model can offer clinicians a novel tool for the precise prediction of MII to guide gonadotropin dosing., (© 2024. The Author(s).)

Background: Recent studies about the effect of gonadotropin (Gn) dose on the clinical outcomes of IVF are still controversial, and no studies have analyzed the relationship between Gn dose and embryo quality. Since AMH is a strong predictor of oocyte quality, we aim to evaluate the relationship between total Gn dose and embryo quality and clinical outcomes at different AMH levels in IVF cycles., Methods: A total of 12,588 patients were enrolled in the retrospective study. The included cycles were categorized by serum AMH levels (AMH ≤ 1 ng/ml, 1 ng/ml < AMH ≤ 3 ng/ml, 3 ng/ml < AMH ≤ 5 ng/ml, AMH > 5 ng/ml), total Gn dosage (< 1875 IU, 1875-3750 IU and ≥ 3750 IU) and female age (< 35 years and 35-42 years). The embryo quality and clinical outcomes were the measure outcomes., Results: The top-day3 embryos rate decreased with the increase of total Gn dose in nearly all age and AMH subgroups, but this trend was not obvious in the AMH > 5 ng/ml group and AMH ≤ 1 ng/ml group. The blastocyst formation rate and high-quality blastulation rate had a negative relationship with Gn does for women aged < 35 years in the AMH ≤ 5 ng/ml groups, except for the AMH > 5 ng/ml group (P < 0.001). However, when women were 35-42 years old, regardless of AMH levels, the blastocyst formation rate and high-quality blastulation rate decreased as Gn dose increased. Clinical outcomes (implantation rate, clinical pregnancy rate and live birth rate) decreased with the increase of Gn dose in all ages and AMH stratifications., Conclusions: The total dose of Gn may have different effects on embryo quality at different serum AMH levels, and the negative effects of total dose of Gn on clinical outcomes may be realized by impairing both embryo quality and endometrium., (© 2024. The Author(s).)

Objective: To determine the ongoing pregnancy rate among patients with infertility with a low antimüllerian (AMH) level compared with those with a normal AMH level after oral and injectable ovulation induction (OI)/intrauterine insemination (IUI)., Design: Retrospective cohort., Setting: Academic center., Patient(s): Patients completing ≥1 medicated OI/IUI cycle at our center between 2015 and 2019 were included. The AMH levels were measured within 12 months of treatment initiation. The cohort was stratified into low AMH (AMH level, <1.0 ng/mL) and normal AMH (AMH level, ≥1.0 ng/mL) groups. All subsequent medicated OI/IUI cycles occurring within 1 year of initial cycle start date were included up to the third completed cycle or until an ongoing pregnancy was recorded. Patients were stratified by age (<35, 35-40, and >40 years), and the relationship between the low and normal AMH groups and each binary endpoint were quantified as risk ratios using the age-adjusted Poisson models., Intervention(s): None., Main Outcome Measure(s): Ongoing pregnancy., Result(s): A total of 3,122 patients completed 5,539 oral antiestrogen cycles, and 1,060 completed 1,630 injectable gonadotropin cycles. For oral antiestrogen treatment, pregnancy outcomes, including ongoing pregnancy rate per cycle, for patients with a low AMH level were comparable with those for patients with a normal AMH level (<35 years, 15.4% vs. 14.9%; 35-40 years, 10.0% vs. 11.0%; and >40 years, 2.8% vs. 3.3%). For injectable gonadotropin treatment, the ongoing pregnancy rate was lower in the low AMH group than in the normal AMH group for the ages of <35 (12.1% vs. 23.5%; relative risk [RR], 0.52 [95% confidence interval {CI}, 0.28-0.97]) and 35-40 (12.5% vs. 18.5%; RR, 0.70 [95% CI, 0.49-0.99]) years but comparable with that for patients aged >40 years (3.0% vs. 4.0%; RR, 0.86 [95% CI, 0.31-2.35]). The proportion of multifetal gestations was similar between the low and normal AMH groups treated with oral antiestrogens (13.1% vs. 10.8%); however, for injectable gonadotropin treatment, patients with a normal AMH level had a higher proportion of multifetal gestations (18.6% vs. 31.1%)., Conclusion(s): Compared with normal ovarian reserve, treatment with oral antiestrogens for OI/IUI for patients with low ovarian reserve results in comparable follicular development and ongoing pregnancy rates for all age groups. When patients with low ovarian reserve are treated with gonadotropins for OI/IUI, multifollicular recruitment is less likely resulting in a significantly decreased ongoing pregnancy rate for patients aged <35 and 35-40 years but also a decrease in multifetal gestations. Overall, the ongoing pregnancy rates of 8.7% per oral antiestrogen cycle and 8.1% per injectable gonadotropin cycle in patients with low ovarian reserve are comparable with the expected rates in the general infertility population., (Copyright © 2022. Published by Elsevier Inc.)

Study Question: Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF?, Summary Answer: In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose., What Is Known Already: Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking., Study Design, Size, Duration: We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre., Participants/materials, Setting, Methods: Women <43 years of age with AFC <10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1-6 started with 300 IU/day, while women with AFC 7-9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks' gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective., Main Results and the Role of Chance: We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99-1.38), risk difference 0.07 (95% CI, -0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83-1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91-1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44-1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer., Limitations, Reasons for Caution: As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results., Wider Implications of the Findings: In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs., Study Funding/competing Interest(s): This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work., Trial Registration Number: Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944., Trial Registration Date: 17 March 2019., Date of First Patient’s Enrolment: 20 March 2019., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The individual response to controlled ovarian stimulation (COS) depends on several factors, including the initial dose of gonadotropin. In repeated in vitro fertilization (IVF) cycles, the initial dose of gonadotropin is mainly established on the basis of the previous attempts' outcomes. Conversely, in naive patients, the ovarian response should be estimated using other criteria, such as the serum concentration of anti-Müllerian hormone (AMH). However, in clinical practice, the initial gonadotropin dose is not systematically adapted to the AMH level, despite the known relationship between AMH and ovarian reserve., Material and Methods: French non-interventional, longitudinal, prospective, multicentre, cohort study that included infertile women who underwent COS with highly purified human menopausal gonadotropin (HP-hMG 600 IU/mL) during their first IVF/intracytoplasmic sperm injection (ICSI) cycle. Data were collected prospectively during routine follow-up visits from COS initiation to 10-11 weeks after embryo transfer., Results: Data from 235 of the 297 enrolled women were used for the study. Serum AMH level was negatively correlated with the initial and total HP-hMG doses (p<0.001), and positively correlated with the number of retrieved oocytes (p<0.007). Embryos were obtained for 94.0% of women, and fresh embryo transfer was performed in 72.8% of them. The clinical pregnancy rate was 28.5% after the first embryo transfer., Conclusion: Selecting the appropriate starting dose of gonadotropin is crucial to optimize the IVF/ICSI procedure. For the first attempt, the serum AMH level is a good biomarker to individualize treatment., Competing Interests: Declaration of Competing Interest Paul BARRIERE, Géraldine PORCU-BUISSON and Catherine AVRIL report personal fees from Ferring SAS, during the conduct of the study., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Aims: This study aimed to explore the value of ovarian reserve tests (ORTs) for predicting poor ovary response (POR) and whether an age cutoff could improve this forecasting, so as to facilitate clinical decision-making for women undergoing in vitro fertilization (IVF)., Methods: A retrospective cohort study was conducted on poor ovary response (POR) patients using real-world data from five reproductive centers of university-affiliated hospitals or large academic hospitals in China. A total of 89,002 women with infertility undergoing their first traditional ovarian stimulation cycle for in vitro fertilization from January 2013 to December 2019 were included. The receiver operating characteristic (ROC) curve was performed to estimate the prediction value of POR by the following ORTs: anti-Mullerian hormone (AMH), antral follicle count (AFC), basal FSH (bFSH), as well as patient age., Results: In this retrospective cohort, the frequency of POR in the first IVF cycle was 14.8%. Age, AFC, AMH, and bFSH were used as predicting factors for POR, of which AMH and AFC were the best indicators when using a single factor for prediction (AUC 0.862 and 0.842, respectively). The predictive values of the multivariate model included age and AMH (AUC 0.865), age and AFC (AUC 0.850), age and all three ORTs (AUC 0.873). Compared with using a single factor alone, the combinations of ORTs and female age can increase the predictive value of POR. Adding age to single AMH model improved the prediction accuracy compared with AMH alone (AUC 0.865 vs. 0.862), but the improvement was not significant. The AFC with age model significantly improved the prediction accuracy of the single AFC model (AUC 0.846 vs. 0.837). To reach 90% specificity for POR prediction, the cutoff point for age was 38 years old with a sensitivity of 40.7%, 5 for AFC with a sensitivity of 55.9%, and 1.18 ng/ml for AMH with a sensitivity of 63.3%., Conclusion: AFC and AMH demonstrated a high accuracy when using ROC regression to predict POR. When testing is reliable, AMH can be used alone to forecast POR. When AFC is used as a prediction parameter, age is suggested to be considered as well. Based on the results of the cutoff threshold analysis, AFC ≤ 5 and AMH ≤ 1.18 ng/ml should be recommended to predict POR more accurately in IVF/ICSI patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Jin, Mao, Shi, Huang, Jiang, Zhang and Liang.)

Objective: To investigate whether minimal ovarian stimulation (mOS) is as effective as conventional ovarian stimulation (cOS) for older women belonging to different groups according to the Poseidon criteria., Material and Methods: Observational retrospective multicentre cohort including women from Poseidon's groups 2 and 4 that underwent in vitro fertilization (IVF). We performed a mixed-effects logistic regression model, adding as a random effect the patients and the stimulation cycle considering the dependence of data. Survival curves were employed as a measure of the cumulative live birth rate (CLBR). The primary outcomes were live birth rate per embryo transfer and CLBR per consecutive embryo transfer and oocyte consumed until a live birth was achieved., Results: A total of 2002 patients underwent 3056 embryo transfers (mOS = 497 and cOS = 2559). The live birth rates per embryo transfer in mOS and cOS showed no significant difference in both Poseidon's groups. Likewise, the logistic regression showed similar live birth rates between the two protocols in Poseidon's groups 2 (OR 1.165, 95% CI 0.77-1.77; p = 0.710) and 4 (OR 1.264 95% CI 0.59-2.70; p = 0.387). However, the survival curves showed higher CLBR per oocyte in women that received mOS (Poseidon group 2: p < 0.001 and Poseidon group 4: p = 0.039)., Conclusions: Minimal ovarian stimulation is a good alternative to COS as a first-line treatment for patients belonging to Poseidon's groups 2 and 4. The number of oocytes needed to achieve a live birth seems inferior in mOS strategy than cOS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations., Results: Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders., Conclusions: The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.

Nearly a century ago, studies by Lancelot Hogben and others demonstrated that ovulation in female Xenopus laevis can be induced via injection of mammalian gonadotropins into the dorsal lymph sac, allowing for egg production throughout the year independent of the normal reproductive cycles. Hormonally induced females are capable of producing thousands of eggs in a single spawning, which can then be fertilized to generate embryos or used as a substrate for generation of egg extracts. The protocol for induction of ovulation and subsequent egg collection is straightforward and robust, yet some of its details may vary among laboratories based on prior training, availability of necessary reagents, or the experimental objectives. As the goal of this protocol is not to describe every single variation possible for acquiring eggs but to provide a simple and clear description that can be easily applied by researchers with no prior working experience with X. laevis , we focus on describing the method we use at the National Xenopus Resource-that is, inducing ovulation in X. laevis via dorsal lymph sac injection of gonadotropic hormones and the stimulation of egg laying through application of gentle pressure to the females., (© 2021 Cold Spring Harbor Laboratory Press.)

Aim: Define how and when fixed starting gonadotropin doses can be used in current clinical ART practices in Italy., Methods: A Delphi conference consisting of three rounds was performed in order to define the ideal clinical conditions in which fixed-gonadotropin-dose during COS should be applied. During the conference, 19 statements about the current ART practice were provided to a panel of twenty-nine national experts. Median score was 5 (IQ:4-6) in all Delphi rounds., Results: Eleven statements (57.9%) were classified as shareable with high-degree of convergence, 2 (10.5%) as shareable with low convergence and 6 (31.6%) as un-shareable with high convergence. The panel reached high consensus regarding some statements: (i) fixed FSH-dose in normoresponders and poor-responder, (ii) importance of predicting ovarian response before COS, considering multiple markers to select the right stimulation protocol for each patient, (iii) importance of therapy simplification and standardization to improve efficiency during COS. Moreover, a low-convergence was reached about use of GnRH antagonist as first treatment line and drug storage at room temperature. However from these findings, the debate remains open regarding some other statements: (a) usefulness of Bologna-criteria to define poor-responders; (b) efficacy to change always stimulation protocol after a failure IVF; (c) utility of AMH-dosed with standardized automatic mode to define normo-responder patients; (d) usefulness to modify the dosage of 12.5 IU/die during COS to improve stimulation effectiveness., Conclusion: Controlled ovarian stimulation remains a challenging clinical step in Assisted Reproductive Technique, especially in some specific patient groups for which no clinical consensus is available. This study is the first attempt to describe the shared clinical opinion regarding the fixed versus variable gonadotropin dose in the real IVF practice.

Purpose: To evaluate the effect of the ejaculatory abstinence period on sperm DNA fragmentation and pregnancy rates in IUI cycles., Methods: One hundred and twenty couples with unexplained infertility were prospectively randomized into two groups on the second day of their cycle. In group A, patients had 1-day ejaculatory abstinence period; in group B patients had 3-day ejaculatory abstinence period. Each patient was stimulated with gonadotropins, and IUI was performed. The primary outcome measure was clinical pregnancy and sperm DNA fragmentation rate., Results: The pregnancy rate was 17.3% and 18.5% in group A and group B, respectively. No significant difference was found among the groups (p = 0.803). The sperm DNA fragmentation rate for group A (20.71 ± 11.01) and group B (23.78 ± 12.64) were almost similar (p = 0.187). The sperm DNA fragmentation rate was 24.89 ± 12.89 in pregnant couples and 21.71 ± 11.69 in non-pregnant couples (p = 0.288)., Conclusion: Even after a short abstinence period of 1 day, compared to the standard abstinence period of 3 days, pregnancy rates are similar among unexplained infertility couples undergoing ovarian stimulation and IUI., Clinicaltrials: The study was registered at ClinicalTrials.gov with ID NCT04361292. Date of registration: 27 April 2020. The study was registered retrospectively.

Objective: To study the association of endometrial thickness (EMT) with live birth rates (LBR) in ovarian stimulation with intrauterine insemination (OS-IUI) treatments for unexplained infertility., Design: Prospective cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial., Setting: Multicenter randomized controlled trial., Patients: A total of 868 couples with unexplained infertility (n=2,459 cycles)., Interventions: OS-IUI treatment cycles (n = 2,459) as part of the AMIGOS clinical trial., Main Outcome Measures: Live birth rates; unadjusted and adjusted risk ratios (RR) for live birth by EMT category, calculated using generalized estimating equations., Results: The overall mean EMT on day of human chorionic gonadotropin administration in cycles with a live birth was significantly greater than in those without. Compared to the referent EMT group of 9 to 12 mm, the unadjusted RR for live birth for the EMT groups of ≤5 and 6-8 were 0.48 and 0.92, respectively. The test for trend indicated evidence of decreasing LBR with decreasing EMT. After adjustment for ovarian stimulation medication, a linear trend was no longer supported. Stratified analyses revealed no differences in associations by treatment group., Conclusions: In OS-IUI for unexplained infertility, higher LBR are observed with increasing EMT; however, EMT is not significantly associated with LBR when adjusted for OS treatment type. Appreciable LBR are seen at all EMT, even those of ≤5 mm, suggesting that OS-IUI cycles should not be canceled for thin endometrium., Clinical Trial Registration Number: NCT01044862., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) are often used to aid fertility in women with endometrioma; however, the implications of endometrioma on ART are unresolved., Objective: To determine the effect of endometrioma on reproductive outcomes in women undergoing IVF or ICSI., Methods: A systematic review and meta-analysis was conducted to identify articles examining women who had endometrioma and had undergone IVF or ICSI. Electronic searches were performed in PubMed, BIOSIS and MEDLINE up to September 2019. The primary outcome was live birth rate (LBR). Secondary outcomes included clinical pregnancy rate (CPR), implantation rate (IR), number of oocytes retrieved, number of metaphase II (MII) oocytes retrieved, number of embryos and top-quality embryos and the duration of gonadotrophin stimulation and dose., Results: Eight studies were included. Where significant heterogeneity between studies was identified, a random-effects model was used. The number of oocytes (weighted means difference; WMD-2.25; 95% CI 3.43 to - 1.06, p = 0.0002) and the number of MII oocytes retrieved (WMD-4.64; 95% CI 5.65 to - 3.63, p < 0.00001) were significantly lower in women with endometrioma versus controls. All other outcomes, including gonadotrophin dose and duration, the total number of embryos, high-quality embryos, CPR, IR and LBR were similar in women with and without endometrioma., Conclusion: Even though women with endometriomas had a reduced number of oocytes and MII oocytes retrieved when compared to women without, no other differences in reproductive outcomes were identified. This implies that IVF/ICSI is a beneficial ART approach for women with endometrioma.

Purpose: The aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation., Methods: We performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed., Results: There were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%)., Conclusions: The use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.

Purpose: To assess the effects PCOS on live birth rates when transferring a single fresh ideal blastocyst., Methods: A retrospective cohort study performed at the university-affiliated reproductive center. Women with PCOS and a control group of normal ovulatory women who underwent their first fresh embryo transfer with single ideal grade blastocyst were included in the study. Demographic, stimulation information and pregnancy outcomes were collected and analysed. The primary outcome was live birth rates, and secondary outcomes included pregnancy and clinical pregnancy rates., Results: 71 Women with PCOS and 272 normal ovulatory controls underwent their first embryo transfer and met the inclusion and exclusion criteria. PCOS patient were younger (31.0 ± 3.7 vs. 33.1 ± 3.2, p = 0.0001), with higher AFC (40.0 ± 9.3 vs. 13.3 ± 4.6, p = 0.0001), required lower dose of gonadotropins to stimulate (1198 ± 786 vs. 1891 ± 1224, p = 0.0001), and had higher serum testosterone levels (2.3 ± 0.7 vs. 1.1 ± 0.3, p = 0.0001). No significant difference was found between the two groups regarding the number of previous pregnancies, the number of previous full-term pregnancies, the level of basal serum FSH, estradiol level at triggering and the BMI. When compared by Chi squared testing pregnancy rates, clinical pregnancy rates and live birth rates did not differ. However, when controlling (with multivariate stepwise logistic regression) for confounders, live birth rates were lower among the women with PCOS (p = 0.035, CI: 0.18-0.92)., Conclusion: After controlling for confounders, when transferring a fresh single ideal blastocyst, live birth rates were lower among the women with PCOS than normal ovulatory controls.

The objective of this study was to evaluate predicting factors for supraphysiologic serum estradiol elevation during controlled ovarian stimulation (COS) with administration of letrozole and gonadotropins in patients with estrogen-dependent cancer. Use of aromatase inhibitors is recommended to prevent the potential effects of elevated serum estradiol levels and recurrence of tumor in patients with estrogen-dependent cancers during COS. Although previous studies reported that letrozole have shown an effective lowering of peak estrogen levels, a part of patients shows supraphysiologic levels of estrogen associated with ovarian stimulation despite the administration of letrozole. From January 2009 to December 2019, patients with estrogen-dependent cancer who underwent COS with antagonist protocol using a letrozole (5 mg/ day) to keep estrogen levels low were included in this study. Early monitoring serum estradiol was measured in all patients on the 4-6th day of stimulation. Subjects were classified into two groups according to the serum estradiol level on hCG triggering day, physiologic estradiol group (≤400 pg/mL) and supraphysiologic estradiol group (>400 pg/mL). A total of 96 COS cycles were retrospectively analyzed. Supraphysiologic level of serum estradiol was found in 21.9% of the patients. Mean age, AMH, duration of stimulation, total dose of gonadotropins administered were not different between the two groups. However, early monitoring serum estradiol level was significantly higher in the supraphysiologic estradiol group (67.1±47.9 vs. 115.6±78.1, p = 0.001) and was associated with the occurrence of supraphysiologic elevation of serum estradiol on hCG triggering day. Patients with early monitoring serum estradiol ≥84.5 pg/mL had an odds ratio of 5.376 [95% CI, 1.613-17.913] for supraphysiologic elevation of serum estradiol compared to those with early monitoring serum estradiol below 84.5 pg/mL. In conclusion, early monitoring serum estradiol is an independent predicting factor for supraphysiologic level of serum estradiol on hCG triggering day in the COS cycles using letrozole and gonadotropins., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We aimed to define intrauterine insemination (IUI) cycle characteristics associated with viable birth, identify thresholds below which IUI treatments are consistent with very poor prognosis and futile care, and develop a nomogram for individualized application., Methods: This retrospective cohort study evaluated couples using fresh partner ejaculate for IUI from January 2005 to September 2017. Variables included female age, semen characteristics, and ovarian stimulation type. Using cycle-level data, we evaluated the association of these characteristics with the probability of viable birth by fitting generalized regression models for a binary outcome with a logit link function, using generalized estimating equation methodology to account for the correlation between cycles involving the same patient., Results: The cohort consisted of 1117 women with 2912 IUI cycles; viable birth was achieved in 275 (9.4%) cycles. Futile care (viable birth rate < 1%) was identified for women age > 43, regardless of stimulation type or inseminate motility (IM). Very poor prognosis (viable birth rate < 5%) was identified for women using oral medications or Clomid plus gonadotropins who were (1) age < 35 with IM < 49%, (2) age 35-37 with IM < 56%, or (3) age ≥ 38, and (4) women age ≥ 38 using gonadotropins only with IM < 60%. A clinical prediction model and nomogram was developed with an optimism-corrected c-statistic of 0.611., Conclusions: The present study highlights the impact of multiple clinical factors on IUI success, identifies criteria consistent with very poor prognosis and futile care, and provides a nomogram to individualize counseling regarding the probability of a viable birth.

Objective: To investigate the effect of gonadotropin (Gn) on embryo aneuploidy rate and pregnancy outcome during preimplanptation genetic testing for aneuploidy (PGT-A) cycles. Methods: The clinical data of patients undergoing PGT-A cycle at the First Medical Center of the PLA General Hospital from January 1, 2013 to May 31, 2019 were retrospectively analyzed. Patients were divided into younger patient group (<35 years old) and elder patient group (≥35 years old) by maternal age, then divided into two groups in line with Gn dosage (≤2 250 U, >2 250 U), and into four groups by number of oocytes retrieved (1-5, 6-10, 11-15 and ≥16 oocytes). The embryo aneuploidy rate and pregnancy outcome between the groups were compared. Logistic regression was used to analyze the relationship between the cumulative amount of Gn, embryo aneuploidy rate and live-birth rate. Results: A total of 402 cycles (338 patients) and 1 883 embryos were included in the study. (1) In the younger patients, the aneuploidy rate was 52.5% (304/579) in the group of Gn≤2 250 U and 48.6% (188/387) in the group of Gn > 2 250 U, with no significant difference between them ( P= 0.232). In the elderly patients, the difference in embryo aneuploidy rate between the two Gn group [57.9% (208/359) versus 60.6% (319/526)] was not statistically significant ( P= 0.420). (2) The embryonic aneuploidy rate in different protocol of ovary stimulation was analyzed,in the younger group, the embryonic aneuploidy rate in patients using antagonist long protocol was 50.3% (158/314), it was 50.0% (121/242) in agonist long protocol, 52.1% (207/397) in agonist short protocol and 6/13 in luteal phase protocol, no statistical difference was found in above groups ( P= 0.923); in the elder group, embryonic aneuploidy rate was 60.8% (191/314) in antagonist protocol, 58.4% (132/226) in agonist long protocol, 59.2%(199/336) in agonist short protocol, 5/9 in luteal phase protocol, respectively,no significant difference was found ( P= 0.938). (3) In the younger patients, the aneuploidy rate in 1-5 oocytes group, 6-10 oocytes group, 11-15 oocytes group and ≥16 oocytes group was 37.9% (11/29), 54.0% (94/174), 52.5% (104/198) and 50.1% (283/565) respectively, no significant difference was found between the groups ( P= 0.652); while in the elder patients, the difference between aneuploidy rate in each retrieved oocytes group [73.6% (89/121), 57.5% (119/207), 56.3% (108/192), 57.8% (211/365)] was statistically significant ( P= 0.046). (4) Logistic regression analysis of age, cumulative dosage of Gn, number of oocytes obtained, and embryo aneuploidy rate showed that there was no association between the amount of Gn and embryo aneuploidy rate ( P> 0.05); the increase in maternal age would increase the risk of aneuploidy rate of embryos, which was statistically significant ( OR= 1.031, 95 %CI : 1.010-1.054, P= 0.004); the increase in oocytes retrived would significantly decrease the risk of aneuploidy ( OR= 0.981, 95 %CI : 0.971-0.991, P< 0.01). (5) There was no significant difference in biochemical pregnancy rate [55.6% (80/144) versus 52.1% (63/121)], clinical pregnancy rate [50.0% (72/144) versus 47.9% (58/121)] and live-birth rate [46.5% (67/144) versus 40.5% (49/121)] between different Gn dosage groups ( P= 0.613, P= 0.738, P= 0.324). The logistic regression analysis showed that the maternal age, the cumulative dosage of Gn, the number of oocytes obtained, and the ovarian stimulation protocol had no effect on the live-birth rate (all P> 0.05). Conclusions: In PGT-A cycle, the dosage of Gn has no association with the embryo aneuploidy rate and pregnancy outcome. In the patients ≥35 years old, the increase in number of oocytes obtained may decrease the risk of aneuploidy. Age is an important factor affecting the embryo aneuploidy in PGT-A cycle.

Introduction: Antimullerian hormone (AMH) strongly correlates with ovarian reserve and response to controlled ovarian stimulation. Emerging data suggests that serum AMH level may also predict ART outcomes. However, AMH is characteristically elevated in PCOS women and it is unknown whether it may predict live birth outcomes in this population., Methods: This was a retrospective cohort study of 184 PCOS women (Rotterdam criteria) who underwent their first fresh IVF/ICSI cycle. Women were divided into 3 groups according to the <25th (low), 25 to 75th (average), or > 75th (high) percentile of serum AMH concentration. Cycle stimulation parameters and reproductive outcomes were compared between groups., Results: Women in the low serum AMH group were older than those in the average or high AMH (p < 0.05), and required greater gonadotropin dose for stimulation compared to the high AMH group (p < 0.05). Women with high AMH had greater testosterone level compared to women in the low or average AMH groups. No differences were noted between groups in terms of maximal E2, oocytes retrieved and fertilization rate. However, low serum AMH women had significantly greater live birth rates (p < 0.05) and showed a trend towards greater clinical pregnancy rates compared to women in the average and high AMH groups (p = 0.09). The significant association of AMH with live birth rate remained after adjusting for age, BMI, day of transfer and number of embryos transferred., Conclusions: In PCOS women, elevated AMH concentrations are associated with hyperandrogenism and lower live birth rates.

Objective: To compare the proportion of women achieving a desired ovarian response following ovarian stimulation when gonadotropin dosing was determined based on antral follicle count (AFC) vs serum anti-Müllerian hormone (AMH) level, in women undergoing in-vitro fertilization (IVF) using the gonadotropin-releasing hormone (GnRH) antagonist protocol., Methods: This was a randomized double-blind trial carried out in a university-affiliated assisted reproduction unit. A total of 200 women undergoing their first IVF cycle using the GnRH-antagonist protocol between April 2016 and February 2018 were randomized to determination of gonadotropin dosing based on either AFC or serum AMH level measured in the pretreatment cycle 1 month before the IVF cycle. Patients underwent IVF as per our center's standard protocol. The proportion of subjects achieving a desired ovarian response, defined as retrieval of six to 14 oocytes, was compared between the two study arms. Subgroup analysis of patients with baseline AFC > 5 and those with baseline AFC ≤ 5 was performed. Concordance in AFC and AMH categorization between the pretreatment cycle and the ovarian-stimulation cycle was assessed using Cohen's kappa (κ)., Results: There was no significant difference in the proportion of patients achieving a desired ovarian response between the AFC (54%) and AMH (49%) groups (P = 0.479). The median number of oocytes retrieved was nine vs seven (P = 0.070), and the median follicular output rate was 0.54 vs 0.55 (P = 0.764) in the AFC and AMH groups, respectively. Similar findings were observed on subgroup analysis of subjects with AFC ≤ 5 and AFC > 5 at the start of ovarian stimulation (P > 0.05 for all comparisons). There was moderate concordance between AFC and AMH measured in the pretreatment cycle and the stimulation cycle (κ = 0.478 and 0.587, respectively)., Conclusion: The proportion of women achieving a desired ovarian response following ovarian stimulation using the GnRH-antagonist protocol is similar when the gonadotropin-dosing algorithm used is based on AFC or serum AMH level. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Background: In recent years, some studies have shown that there is a positive association between the number of oocytes retrieved and the cumulative live birth rate (CLBR) after fresh and frozen cycles of one oocyte retrieval. However, almost no studies have examined the association between the number of oocytes retrieved and the CLBR when using the "freeze-all" strategy. We performed this study to investigate the effects of an extreme oocyte yield during the first "freeze-all" cycle on the cumulative live birth rate among patients younger than 35 years old., Methods: This was a retrospective cohort study performed in a university-affiliated reproductive medicine centre. Data obtained from 3276 women aged younger than 35 years who underwent their first "freeze-all" cycle (IVF/ICSI) were collected between January 2009 and December 2016. In all, 5025 frozen cycles took place during the follow-up period from January 2009 to December 2018. Patients were divided into five groups according to oocytes retrieved (group 1: 4-10 oocytes; group 2: 11-20 oocytes; group 3: 21-30 oocytes; group 4: 31-40 oocytes; group 5: > 40 oocytes). The primary outcome was the cumulative live birth rate., Results: Unadjusted results showed that the cumulative live birth rate significantly increased as the number of oocytes retrieved increased and reached up to 93.82% in cases with yields of 21-30 oocytes (P < 0.05), after which it did not have a significant increase (P > 0.05). After adjusting for confounders, our results showed that the number of oocytes retrieved is an independent positive predictor of cumulative live birth rate when using a "freeze-all" strategy. (P < 0.001). In addition, the fertilization rate and the gonadotropin dose also influenced the cumulative live birth rate (P<0.05)., Conclusions: Among women younger than 35 years old who underwent the "freeze-all" strategy, the number of oocytes retrieved positively correlated with the cumulative live birth rate. Taking both efficacy and safety into account, ovarian stimulation should be rational, and the upper limit of the oocyte yield should be no more than 30.

Objective: To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI) with oral medications versus gonadotropins., Design: Systemic review and meta-analysis., Setting: Not applicable., Patient(s): Patients undergoing OS-IUI for treatment of unexplained infertility., Intervention(s): Clomiphene, letrozole, or gonadotropins for OS-IUI., Main Outcome Measure(s): Live birth and multiple gestation., Result(s): Eight total trials were identified that met the inclusion criteria and comprised 2,989 patients undergoing 6,590 cycles. One study reported a significant increase in both live births and multiple gestations with the use of gonadotropins, two studies found an increased likelihood of live birth with the use of gonadotropins, and two studies found an increased risk of twins with gonadotropins. The relative risk of live birth in subjects receiving gonadotropins was 1.09. The relative risk of multiple gestation in subjects receiving gonadotropins was 1.06. Clinical pregnancy was higher in protocols with lax cancellation policies or higher gonadotropin doses, with subsequent increased relative risks of multiple gestations of 1.20 and 1.15, respectively. Singleton births per subject were similar between the two groups. The results did not change in per-protocol, per cycle, or fixed-effect model sensitivity analyses., Conclusion(s): For every birth gained with the use of gonadotropins, a similar increased risk of multiple gestation occurs. The randomized data do not support the use of gonadotropin for OS-IUI in women with unexplained infertility., Clinical Trial Registration Number: Prospero CRD4201911998., (Published by Elsevier Inc.)

This document reviews gonadotropin treatment for ovulation induction in anovulatory women and outlines the recommended pretreatment evaluation, indications, treatment regimens, and complications of gonadotropin treatment. It replaces the document with a similar name, last published in 2008 (Fertil Steril 2008;90:S7-12)., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin-stimulated in vitro fertilization compared with spontaneously conceived children: parental factors (age, health, duration of subfertility and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn being small-for-gestational-age., Material and Methods: We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin-stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, adjusted for gestational age and sex., Results: The proportion of small-for-gestational-age was 11.8% following conventional gonadotropin-stimulated in vitro fertilization and 2.9% after natural cycle in vitro fertilization (P = 0.058). The odds of small-for-gestational-age were significantly higher with supraphysiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35-15.55; P = 0.015). It remained significant after adjusting for maternal height, age and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06-13.82; P = 0.041)., Conclusions: We found an associated risk of children being born small-for-gestational-age after conventional gonadotropin-stimulated in vitro fertilization compared with natural cycle in vitro fertilization. This higher risk is significantly associated with supraphysiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small-for-gestational-age and future health consequences., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Purpose: To present the first case proposing the use of preimplantation genetic testing for monogeneic disorders for Kallmann syndrome, providing comprehensive care in the genomic era of precision medicine., Methods: Gonadotropin therapy was used for spermatogenesis, followed by in vitro fertilization by intracytoplasmic sperm injection and embryo transfer. Cross-generational targeted next-generation sequencing was then done for genes known to cause Kallmann syndrome., Results: A heterozygous mutation at codon 102 of the FGFR1 gene was found in the patient, but the father was found to have the same mutation yet is unaffected by Kallmann syndrome. Since no causative mutation was found, a de novo or sporadic mutation was suspected as the cause of Kallmann syndrome in this case., Conclusions: Comprehensive care must be available for male Kallmann syndrome patients, as treatment should not stop at spermatogenesis, but continue with genetic counseling due to possible inheritance.

Purpose: Empirical treatment options for unexplained infertility treatment include controlled ovarian stimulation (COS) with clomiphene citrate, letrozole or gonadotropins followed by intrauterine insemination (IUI). Achieving consistent multifollicular development with letrozole generally requires addition of gonadotropins. However, the cost and discomfort of injections remains a drawback of this regimen. Therefore, there is a need for evolving newer cost-effective regimens for COS/IUI using orally administered drugs like letrozole., Methods: Sixty couples with unexplained infertility (on standard infertility investigations) visiting the infertility clinic at a tertiary centre in North India were randomized into two groups. Group A COS was done by step-up protocol of letrozole from day 2 or 3 of menstrual cycle, starting with 2.5 mg and increased by 2.5 mg per day for next 3 days (2.5 mg, 5 mg, 7.5 mg, 10 mg). Group B COS was done with combination of letrozole and hMG (human menopausal gonadotropin). Starting from day 2 or 3 of menses, tablet letrozole 2.5 mg twice a day was given for 5 days. Intramuscular injection of hMG 150 IU was given every alternate day starting from day 7 and titrated according to the response. HCG was given when leading follicle was 17 mm and IUI done 36 h after HCG., Results: Twenty-eight couples in letrozole step-up group (group A) and 30 couples in letrozole plus hMG group (group B), completed follow up for 44 and 55 cycles, respectively. Mean numbers of follicle ≥ 16 mm in both groups were comparable: 1.74 (± 0.83) in group A and 1.94 (± 0.68) in group B (p = 0.178). Ovulation rate of 90.9% (40/44) was achieved in group A, whereas it was 100% (55/55) in group B (p = 0.022), although there was no significant difference in clinical pregnancy rate per patient, which was 3/28 (10.7%) in group A versus 5/30 (16.67%) in group B (p = 0.707). The mean (SD) cost of medicines was significantly lower in group A Rs. 345.00 (00) compared to group B Rs. 2148.64 (515.67) [p < 0.0001]. There was one case each of hyperstimulation and multiple pregnancies in group B, while none in group A., Conclusion: It is possible to achieve multifollicular development with use of novel letrozole step-up protocol, even without addition of gonadotropins, at significantly lower cost.

Background To determine whether a minimal stimulation (MS) or high-dose stimulation (HDS) protocol is a better option for patients classified as poor ovarian responders (POR) in terms of reproductive and pregnancy outcomes. Materials and methods A database search for evaluation of the study outcome by using meta-analysis method was carried out. The primary outcome was the clinical pregnancy (CP) rate for each of two groups, namely, the MS and HDS groups. The secondary outcomes were the gonadotropin dose used, duration of stimulation, cancellation rate, number of oocytes retrieved, number of fertilized oocytes, number of embryos transferred and live birth rates. Results Across five databases, 4670 potential studies for further screening were selected. But ultimately only six studies, three RCTs and three retrospective or case control studies were selected that meet the Bologna criteria for POR. In all there were 624 cycles. Our meta-analysis indicated that the CP rates, cycle cancellation rates, durations of stimulation, numbers of oocytes fertilized and numbers of embryos transferred were not statistically significant. Clearly, the number of oocytes retrieved in the MS group was significantly lower than in the HDS group, while the HDS group consumed significantly higher doses of gonadotropins than the MS group. The live birth rates were significantly higher in the MS group than in the HDS group. Conclusion MS should be the first-line protocol for managing POR because the live birth rate is significantly higher, even with fewer oocytes retrieved.

Background: The underlying cause of seasonal infertility in humans is unclear, but is likely to be -multifactorial., Objective: The aim of our study was to compare the pregnancy rates among infertile women who underwent induced ovulation and intrauterine insemination (IUI) with the season in which the fertility treatment was performed., Design and Setting: This retrospective cohort study was conducted on 466 patients who were treated in the reproductive endocrinology and infertility outpatient clinic of a tertiary-level women's healthcare and maternity hospital., Methods: Retrospective demographic, hormonal and ultrasonographic data were obtained from the patients' medical records. Clomiphene citrate or gonadotropin medications were used for induced ovulation. The patients were divided into four groups according to the season (spring, winter, autumn and summer) in which fertility treatment was received. Clinical pregnancy rates were calculated and compared between these four groups., Results: There were no significant differences between the seasonal groups in terms of age, infertility type, ovarian reserve tests, duration of infertility, medications used or length of stimulation. A total of 337 patients (72.3%) were treated with clomiphene citrate and 129 (27.7%) with gonadotropin; no significant difference between these two groups was observed. The clinical pregnancy rates for the spring, winter, autumn and summer groups were 15.6% (n = 24), 8.6% (n = 9), 11.5% (n = 13) and 7.4% (n = 7), respectively (P = 0.174)., Conclusions: Although the spring group had the highest pregnancy rate, the rates of successful IUI did not differ significantly between the seasonal groups.

Research Question: Conception via assisted reproductive technology (ART) increases the risk of type 2 diabetes and cardiovascular disease in adulthood. Underlying differences between ART-conceived and in-vivo-conceived embryos that contribute to this increased risk are, however, not known., Design: This study examined the developmental characteristics of mouse blastocysts derived from ART- compared with in-vivo-conceived embryos. To determine the effect of ovarian stimulation versus IVF versus in-vitro embryo culture on phenotype, six distinct groups of blastocysts were generated. Female mice were naturally cycling or treated with high or mild doses of gonadotrophin, followed by natural mating or IVF under clinical conditions. Embryo morphokinetics were assessed by continuous time-lapse monitoring. Cell lineage allocation to the inner cell mass (Oct4+) or trophectoderm (Cdx2+) was determined by immunohistochemistry, and mitochondrial DNA (mtDNA) copy number was measured by quantitative PCR., Results: Ovarian stimulation increased embryo number but reduced the percentage of blastocysts. Morphokinetic analysis showed that gonadotrophin treatment led to advanced development (P < 0.05) due to earlier post-pronuclear breakdown. The blastocyst rate was reduced in IVF embryos compared with those fertilized in vivo before culture (P < 0.001). Morphokinetics showed that embryo development was slower in all the IVF groups (P < <0.05), due to a delay from the 3-cell stage. A reduced total and trophectoderm cell number was observed in all groups of cultured blastocysts compared with naturally conceived blastocysts (P < 0.01). Gonadotrophin treatment did not affect the blastocyst mtDNA copy number; however, IVF embryos exhibited reduced mtDNA copy number compared with naturally conceived embryos., Conclusion: Ovarian stimulation, IVF and in-vitro culture differentially impair blastocyst developmental kinetics, differentiation and mtDNA copy number., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: With a high incidence of insulin resistance, central obesity and dyslipidemia, women with polycystic ovary syndrome are susceptible to metabolic syndrome (MetS). Our objective was to explore whether metabolic syndrome had an effect on overall female fertility and in vitro fertilization outcomes in infertile women with polycystic ovary syndrome., Study Design: This was a secondary analysis of a multicenter randomized trial in 1508 women with polycystic ovary syndrome, which was originally designed to compare the live birth rate after fresh-embryo transfer vs frozen embryo transfer (Frefro-PCOS). At baseline, metabolic parameters, including body mass index, waist and hip circumference, blood pressure, lipid profile, fasting, and 2 hour glucose and insulin levels after a 75 g oral glucose tolerance test were measured. All subjects were divided into a metabolic syndrome group (metabolic syndrome) and absence of metabolic syndrome group (nonmetabolic syndrome) according to diagnostic criteria. Descriptive statistics and logistic regression models tested the association between metabolic syndrome and overall fertility and in vitro fertilization cycle stimulation characteristics and clinical outcomes., Results: Metabolic syndrome was identified in 410 of 1508 infertile women with polycystic ovary syndrome (27.2%). Patients with metabolic syndrome had longer infertility duration (4.0 ± 2.2 vs 3.7 ± 2.2, P = .004) compared with those without metabolic syndrome. During ovarian stimulation, those with metabolic syndrome required significantly higher and longer doses of gonadotropin and had lower peak estradiol level, fewer retrieved oocytes, available embryos, a lower oocyte utilization rate, and ovarian hyperstimulation syndrome than those with nonmetabolic syndrome. The cumulative live birth rate did not show a significant between-group difference (57.8% vs 62.2%, P = .119). Multivariate logistic regression analysis adjusted for age, duration of infertility, body mass index, thyroid-stimulating hormone, metabolic syndrome group, homeostatic model assessment of insulin resistance, metformin utilization, number of available embryos, and embryos transferred showed that the number of embryos transferred and the number of available embryos were positively but metabolic syndrome negatively associated with the cumulative live birth rate (odds ratio, 2.18, 1.10, and 0.70, respectively, P < .05)., Conclusion: Women with polycystic ovary syndrome with metabolic syndrome have a negative impact from female fecundity, and this suggests an adverse effect on in vitro fertilization cycle stimulation characteristics and clinical outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication in women undergoing induction of ovulation with human chorionic gonadotropin (hCG) for assisted reproductive techniques. Amphiregulin (AREG) is the most abundant epidermal growth factor receptor (EGFR) ligand expressed in human granulosa cells and follicular fluid and can be upregulated by luteinizing hormone (LH)/hCG. However, whether the expression levels of AREG, EGFR, and HER2 change in the granulosa cells of OHSS patients remains unknown. If it does, whether these molecules are involved in the development of OHSS requires investigation. In the present study, we showed that AREG, EGFR, and HER2 transcripts in granulosa cells as well as follicular fluid AREG proteins were elevated in OHSS patients. Increased AREG levels were associated with transcript levels and follicular content of vascular endothelial growth factor (VEGF), the marker for OHSS pathology. Treatment of cultured granulosa cells with AREG stimulated VEGF expression and secretion, with granulosa cells from OHSS patients showing more rapid and pronounced increases than the non-OHSS group. In addition, siRNA-mediated knockdown of EGFR and AREG attenuated the hCG-induced upregulation of VEGF. This study demonstrated that granulosa cell-secreted AREG plays an important role in the development of OHSS, suggesting that the EGFR/HER2-mediated signaling could be a novel drug target for the prevention and treatment of OHSS., (© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Although oocyte donors are young and are expected to provide a high rate of euploid oocytes, significant differences of euploidy rates for donor embryos exist between different IVF centers (1). Laboratory conditions can lead to differences of euploidy (2,3,4,5,6,7); but, the role of COH has not been investigated. In this study, we investigated whether euploidy rates in the embryos created from donor oocytes are influenced by controlled ovarian hyperstimulation parameters used during assisted reproduction. Euploidy rates in egg donor cycles undergoing PGT-A (N = 423) were examined retrospectively for associations with donor age, gonadotropin doses (dose per day), the fraction of gonadotropin provided by hMG (F(hMG)), days of stimulation, estradiol per mature oocyte on day of trigger, number of mature oocytes retrieved, number of embryos biopsied, incidence of euploidy and physician of record. Differences in euploidy rates between physicians were examined using analysis of variance. The proportion of euploid embryos per donor cycle was examined for associations with COH parameters using pairwise post-hoc comparisons, adjusting for multiple testing. The set of variables from this analysis was then submitted to a principal component analysis. Linear regression analysis was used to assess the relationships between stimulation parameters and the incidence of euploidy (the dependent variable). Euploidy rates and cycle parameters varied significantly among treating physicians. Euploidy rates (expressed as a fraction of biopsied embryos) were associated (p = 0.01) only with the F(hMG) but not with the number of MII retrieved or other variables. On the other hand, the number of euploid embryos (in contrast to the euploidy rate) was associated with the number of MII produced. Donor euploidy rates are significantly associated with the fraction of total gonadotropin comprising human menopausal gonadotropin (or F(hMG)) during controlled ovarian hyperstimulation but are not associated with other cycle parameters. The study provides the first suggestion that patient stimulation parameters can affect the incidence of euploidy in embryos generated through the use of standard assisted reproductive techniques. The study is limited by its retrospective approach and because the aCGH analysis used is less sensitive than more recent NGS technology. Further, it provides a suggestion that the use of hMG is beneficial for obtaining euploid embryos., (Copyright © 2019. Published by Elsevier Masson SAS.)

Purpose: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear., Patients and Methods: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors., Results: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40-2.39) and 0.90 (95% CI: 0.33-2.41) in singletons and twins, respectively., Conclusion: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks., Competing Interests: The authors report no conflicts of interest in this work.

Objective: To investigate the effect of high body mass index and polycystic ovarian syndrome alone or both on the outcome of in vitro fertilisation-embryo transfer., Methods: The retrospective study was conducted at the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China, and comprised data from August 2015 to November 2016 of infertility patients with polycystic ovarian syndrome or tubal factors who underwent agonist long-protocol in vitro fertilisation-embryo transfer. Group A comprised polycystic ovarian syndrome patients who were further divided into normal weight A1 and overweight A2. Group B had tubal patients who were further divided into normal weight B1 and overweight B2. SPSS 16 was used for data analysis., Results: Of the 428 patients, 153 were in Group A and 275 in Group B. Further, Group A1 had 94(61.44%) patients and Group A2 had 59(38.56%) (p<0.01), while Group B1 had 219(81.64%) and Group B 56(18.36%) patients. The dose of gonadotropins and the duration of stimulation were significantly greater in Group A2 than Group A1(p<0.01), but there was no statistically significant difference in the tubal groups (p>0.05). Significantly more retrieved oocytes and high-quality embryos were observed in the Group A1 (p<0.01). The difference of the maturating rate, fertilisation rate, implantation rate, pregnancy rate and early abortion rate were not significant among the groups (p>0.05).., Conclusions: Polycystic ovarian syndrome with high body mass index had a negative effect on the ovarian response to gonadotropins. Pregnancy outcomes were not influenced by body mass index in tubal patients.

Anti-Müllerian hormone (AMH) has become one of the most informative biochemical markers of the ovary and is considered the earliest and most sensitive marker of reproductive aging. The accuracy of AMH in predicting ovarian response to controlled ovarian stimulation has led to AMH-based prognostication counseling and individualization of assisted reproductive technology (ART) stimulation protocols to optimize ovarian response and minimize hyperstimulation risks. Although AMH is considered a good predictor of quantitative ART outcomes, its correlation with qualitative ART outcomes is still controversial. The aim of this review is to provide an updated overview of the clinical utility of AMH in predicting ART outcomes.

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ± 2730 and the mean number of retrieved oocytes was 19.7 ± 7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases., (Copyright © 2019. Published by Elsevier B.V.)

The initiation and maintenance of reproductive capacity in humans is dependent on pulsatile secretion of the hypothalamic hormone GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies. CHH is characterized by rich genetic heterogeneity, with mutations in >30 genes identified to date acting either alone or in combination. CHH can be challenging to diagnose, particularly in early adolescence where the clinical picture mirrors that of constitutional delay of growth and puberty. Timely diagnosis and treatment will induce puberty, leading to improved sexual, bone, metabolic, and psychological health. In most cases, patients require lifelong treatment, yet a notable portion of male patients (∼10% to 20%) exhibit a spontaneous recovery of their reproductive function. Finally, fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in most patients. In summary, this review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management, and genetic foundations of CHH relative to normal reproductive development., (Copyright © 2019 Endocrine Society.)

To study whether unoperated ovarian endometrioma(s) or its surgical excision led to a modified pattern of ovarian decay with increasing female age. A sectional analysis of basal follicle stimulating hormone (FSH) and ovarian response to gonadotropins was conducted on women treated with fresh autologous In Vitro Fertilization/Intracytoplasmic sperm injection (IVF/ICSI) cycles. The study group included patients with unoperated ovarian endometrioma(s) (108 cycles); control groups were women with previous surgery for monolateral ovarian endometrioma (101 cycles), surgery for bilateral ovarian endometriomas (39 cycles), and tubal factor infertility (171 cycles). Simple linear regression analyses and the Pearson correlation were used to analyze the correlation between basal FSH, number of dominant follicles, number of retrieved oocytes, and age of patients. The relationship between the variables was significant in case of patients with nonoperated ovarian endometrioma(s) and patients with previous surgery for monolateral endometrioma and tubal factor infertility group. In patients with a history of surgery for bilateral endometriomas, no relationship was found among the variables (basal FSH 95% confidence interval [CI]: -0.475 to 0.319; P = .688; number of dominant follicles 95% CI: -0.484 to 0.382; P = .808; number of retrieved oocytes 95% CI: -0.478 to 0.370, P = .792). In women with unoperated ovarian endometrioma(s) or with a history of surgery for monolateral endometrioma, the remaining ovarian parenchyma maintains the same pattern of ovarian decay as healthy ovaries. Unoperated ovarian endometriotic lesions did not interfere with ovarian reserve and IVF/ICSI cycles' outcomes and were less injurious than surgery. After surgery for bilateral ovarian endometriomas, a decline in ovarian reserve seems independent from the patient's age.

Objective: Traditional Chinese medicine (TCM) is an effective management to infertility. The association between TCM-mediated fertility and inhibition of phosphatidylinositol-3-kinase (PI3K) would be investigated., Methods: Institute of Cancer Research mice were treated with three herbal decoctions, named Wenshen Yangxue formula, Wenshen formula, and Yangxue formula, plus with human gonadotropins. PI3K inhibitor wortmannin was administrated to half of mice. Some index such as body weight, fertility ability would be investigated. The expression of P13K/Akt signaling was detected by using Western blot analysis., Results: No difference was observed in body weight among groups. Mice receiving the administration of human gonadotropins and herbal decoctions showed increased follicle numbers, percentage of fertilization, and promoted embryonic development. The treatment of Wenshen Yangxue formula decoction showed the highest efficiency, significant higher than Wenshen and Yangxue formulas. And increased the expression of p-PI3K and p-Akt proteins., Conclusion: These results suggested the herbal decoctions promoted the fertilization of mice, which was related to the charge of PI3K/Akt activation., (© 2018 Wiley Periodicals, Inc.)