Ovarian Hyperstimulation Syndrome Research Articles

Identification and Characterization of Novel FSHR Copy Number Variations Causing Premature Ovarian Insufficiency.

Follicle stimulating hormone (FSH) is a key pituitary gonadotropic hormone implicated in human fertility and is crucial for folliculogenesis and recruitment of new antral follicles. Variations in its receptor, FSHR, can lead to diverse reproductive phenotypes including ovarian hyperstimulation syndrome (OHSS) and premature ovarian insufficiency (POI). This study reports a novel case of FSHR-related ovarian insufficiency in a patient with primary amenorrhea, subnormal AMH levels, and delayed puberty. Genetic exploration revealed two compound heterozygous intragenic deletions of FSHR. Specifically, the patient inherited a maternally derived deletion spanning exons 5-10 and a paternally derived deletion involving exons 3-6. Through chromosomal microarray analysis (CMA), exome sequencing, long-range PCR, and Sanger sequencing, we characterized the breakpoints and confirmed the compound heterozygous deletions. The findings reveal a complete loss of function of both FSHR alleles, contributing to the patient's POI phenotype. This case emphasizes the complexity of genotype-phenotype correlations in FSHR-related disorders and the role of CNVs in POI phenotypes. Although these events are rare, our results advocate for the inclusion of CNV detection in the diagnostic workup of POI to ensure accurate diagnosis and better patient management.

Triggering oocyte maturation in IVF treatment in normal responders: a systematic review and network meta-analysis.

To compare efficacy and safety of hCG, GnRH agonist, dual, and double triggers in predicted normal responders undergoing ovarian stimulation and IVF DESIGN: A systematic review and network meta-analysis of randomized controlled trials (RCTs). RCTs indexed in PubMed, MEDLINE, EMBASE, clinical trial registries and Cochrane Database of Systematic Reviews up to December 2023. Twelve high-integrity RCTs comprising 1,931 women were included, which compared hCG trigger to GnRH agonist trigger, dual trigger, and double trigger. Statistical analysis was performed using STATA version 16. Key outcomes included clinical pregnancy rates (CPR), live birth rates (LBR), number of oocytes, number of mature oocytes, miscarriage rate and rates of ovarian hyperstimulation syndrome (OHSS). The network meta-analysis for CPR were relative risk (RR) 1.13 (95% Confidence Interval (CI):0.80-1.60) for hCG versus GnRH agonist trigger, RR 1.23 (95% CI:0.92-1.65) for hCG versus dual trigger, RR 0.38 (95% CI:0.21-0.69) for hCG versus double trigger, RR 1.09 (95% CI:0.70-1.70) for GnRH agonist versus dual trigger and 0.34 (95% CI:0.17-0.67) for GnRH agonist versus double trigger and RR 0.31 (95%CI:0.16-0.60) for double versus dual trigger. Dual trigger demonstrated the highest SUCRA (85.1%), indicating superior efficacy for clinical pregnancy rates. For LBR, while connectivity was limited, the RR was 1.31 (95% CI: 1.00-1.70) for dual versus hCG trigger, and RR 1.60 (95% CI: 1.05-2.43) for dual versus GnRH agonist trigger. OHSS rates were significantly lower with the GnRH agonist compared to hCG trigger (RR 0.56, 95% CI: 0.19-1.75). There were no randomized controlled trials reporting OHSS rates with the use of dual or double trigger. No significant differences were observed in the number of oocytes retrieved, mature oocytes, or miscarriage rates among the trigger protocols. The findings indicate that there is no evidence to suggest that using GnRH agonist, dual, or double protocols is superior to hCG trigger in improving clinical pregnancy rates. While live birth rates may benefit from dual trigger, results are limited by available RCTs. Larger, multicentre trials are needed for further evaluation of live birth rates and understanding of long-term outcomes.

Enhancing IVF Outcomes with Artificial Intelligence: Current Advances and Future Possibilities

The integration of Artificial Intelligence (AI) into In Vitro Fertilization (IVF) practices has marked a revolutionary shift in reproductive medicine, offering enhanced precision, efficiency, and personalized treatment plans. The rapid advancement of Artificial Intelligence (AI) has led to significant innovations in the field of reproductive medicine, particularly in In Vitro Fertilization (IVF). Traditional IVF procedures, while effective, often face challenges such as variable success rates, high costs, and the emotional burden on patients due to multiple treatment cycles. AI offers a promising solution to these issues by enhancing accuracy, personalization, and efficiency throughout the IVF process. AI algorithms have shown remarkable capabilities in diagnosing infertility by analyzing complex datasets from hormone profiles, genetic testing, and medical imaging, enabling early identification of conditions like polycystic ovary syndrome (PCOS) and endometriosis. Moreover, one of the most promising applications of AI in IVF is embryo grading. However, AI systems have been developed to objectively evaluate embryos based on time-lapse imaging, morphology, and other parameters, improving the selection process. Additionally, AI has been instrumental in optimizing ovarian stimulation protocols by analyzing patient data to determine the appropriate medication dosage, minimizing the risk of ovarian hyperstimulation syndrome (OHSS). This review discusses the current state of AI integration in fertility treatments, successful case studies, and ongoing research to develop more sophisticated AI models. Overall, AI holds immense promise in making IVF more accessible, affordable, and successful for patients worldwide, ushering in a new era of precision medicine in reproductive health.

Lupus activity and pregnancy outcomes in systemic lupus erythematosus patients undergoing assisted reproductive therapy: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. While pregnancy and hormonal stress can trigger SLE flare-ups, the effects of assisted reproductive therapies (ARTs) on SLE patients are not well defined. We conducted a search of PubMed/Medline, Embase, and CENTRAL until March 20, 2024, to find observational studies assessing the prevalence of SLE flares and pregnancy outcomes following ARTs. Our analysis included random-effects meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for evaluating evidence quality. Five studies involving 237 SLE women who underwent ARTs were eligible. The meta-analysis indicated a prevalence of SLE flares at 17% (95% CI: 10-25%) with moderate-quality evidence. The pooled prevalence of arthritis flares was 7% (95% CI: 0-25%) with low-quality evidence. Successful pregnancy rates were 58% (95% CI: 43-72%), and live birth rates were 96% (95% CI: 83-100%), both with low-quality evidence. Moderate-quality evidence showed pregnancy complications, including preterm premature rupture of membranes (PPROM) at 8% (95% CI: 3-16%), miscarriages at 2% (95% CI: 0-9%), intrauterine fetal demise (IUFD) at 4% (95% CI: 0-11%), and preeclampsia at 7% (95% CI: 1-17%). Low-quality evidence showed preterm labor at 10% (95% CI: 0-32%) and ovarian hyperstimulation syndrome (OHSS) at 2% (95% CI: 0-11%). SLE flares, as well as pregnancy complications such as IUFD, miscarriage, PPROM, and preeclampsia in ART recipients, are equivalent to those in spontaneous conception. This indicates that ART is relatively safe for SLE patients with meticulous pregnancy planning. Key Points •Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily impacting women of childbearing age. • Pregnancy in women with SLE poses elevated maternal and fetal risks compared to healthy women. • SLE flares and pregnancy complications while receiving ART are equivalent to those in spontaneous conception and ART is relatively safe for SLE patients.

In vitro maturation of oocytes: what is already known?

Assisted reproductive technologies (ARTs) involve the laboratory manipulation of gametes and embryos to help couples with fertility problems become pregnant. One of these procedures controlled ovarian stimulation uses pharmacological agents to induce ovarian and follicular maturation in vivo. Despite the effectiveness in achieving pregnancy and live births, some patients may have complications due to over-response to gonadotropins and develop ovarian hyperstimulation syndrome (OHSS). In vitro maturation of oocytes (IVM) has emerged as a technique to reduce the risk of OHSS, particularly in women with polycystic ovary syndrome (PCOS), and for fertility preservation in women undergoing oncological treatment. Although there are some limitations, primarily due to oocyte quality, recent advances have improved pregnancy success rates and neonatal and infant outcomes. Different terms have been coined to describe variations of IVM, and the technique has evolved with the introduction of hormones to optimize results. This review we provide a comprehensive overview of IVM and its reproductive outcomes during ARTs.

Fixed versus flexible gonadotropin releasing hormone antagonist protocol in women with polycystic ovary syndrome undergoing in vitro fertilization: An RCT.

Despite the extensive use of the gonadotropin-releasing hormone (GnRH) antagonist protocol in treating infertile women, particularly those with polycystic ovary syndrome (PCOS), there have not been sufficient evidence to compare the flexible and fixed variants in in vitro fertilization (IVF) cycles. This study aims to assess the treatment outcomes of flexible and fixed types of GnRH-antagonist protocol for IVF in women with PCOS. In this randomized clinical trial, 150 infertile women with PCOS, who were candidates for IVF, and referred to the Yazd Research and Clinical Center for Infertility, Yazd, Iran between October 2023 and February 2024 were included. Participants were divided into 2 groups (n = 75/each) based on the type of antagonist protocol (fixed or flexible). GnRH antagonist administration started on the 5 day of gonadotropin treatment in the fixed group. In the flexible group when there was at least one follicle 12-14 mm, GnRH antagonist was started. Finally, the number of metaphase II oocyte, the quality of embryos, the duration of the stimulation cycle, the dose of gonadotropin, the number of GnRH-antagonist, and the rate of ovarian hyperstimulation syndrome were evaluated. No statistically significant difference was observed in terms of cycle length and the total dose of gonadotropin between groups. Nevertheless, a notable distinction was observed in the total number of oocytes (17.84 vs. 15.5, p = 0.023) and mature oocytes (13.64 vs. 11.83, p = 0.019) in the flexible group compared to the fixed group. In conclusion, the IVF outcomes are more favorable in women with PCOS undergoing the flexible GnRH-antagonist protocol compared to the fixed protocol.

Case 330: Ovarian Torsion in the Setting of Ovarian Hyperstimulation Syndrome.

A 30-year-old female patient with a history of infertility and no pregnancy presented to the gynecologic endometriosis clinic for follow-up 1 month after oocyte retrieval, to be evaluated for pelvic optimization before potential embryo transfer, with worsening dysmenorrhea, dyspareunia, and overall pelvic pain. Eleven years prior, the patient had undergone left ovarian cystectomy for treatment of endometrioma, as well as excision of deep infiltrating endometriosis. The oocyte retrieval procedure, where more than 30 eggs were retrieved, was complicated by ovarian hyperstimulation syndrome and intraperitoneal bleeding, which necessitated admission to the intensive care unit (ICU) for 3 days. Following discharge from the ICU, the patient experienced occasional on-and-off pressure of the urinary bladder and persistent aching pelvic pain.

The best evidence for the management of ovarian hyper-stimulation syndrome in patients undergoing assisted reproductive therapy

To summarize the best evidence for the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy. Evidence related to the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy, including guidelines, clinical decision, best clinical practice, systematic evaluation, expert consensus and evidence summary and related original research were systematically searched in UpToDate, BMJ Best Practice, World Health Organization (WHO) website, Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE) website, National Guidelines website, American Society for Reproductive Medicine (ASRM) website, New York Academy of Sciences (NYAS) website, Joanna Briggs Institute (JBI) database, Cochrane Library, CINAHL, PubMed, Wanfang database, CNKI, and China Biomedical Literature Database from inception to May 31, 2024. Two researchers independently evaluated the quality of the literature, and a senior researcher made the final decision for literature inclusion. A total of 15 articles were included in the study. Following quality assessment, one article was excluded. The remaining 14 articles included 5 practice guidelines, 3 systematic reviews, 2 expert consensuses, 1 evidence summary, and 3 from UpToDate. Ultimately, 27 pieces of evidence were identified across five key aspects: risk assessment, disease monitoring, early prevention, institutional management and health education. The updated evidence indicates that the monitoring and prevention of ovarian hyperstimulation syndrome should start early, personalized treatment plans should be provided for patients, and the rational allocation of treatment resources needs to be promoted to enhance effective management of ovarian hyper-stimulation syndrome.

Ischemic events are infrequent in patients with ovarian hyperstimulation syndrome

BackgroundCase reports describe arterial thrombosis including ischemic stroke associated with severe ovarian hyperstimulation syndrome (OHSS), but the prevalence of major ischemic events during or shortly after OHSS is unknown. MethodsUsing publicly available administrative datasets in the United States between 2015 and 2020, we conducted two separate cross-sectional studies of patients with OHSS. We included all patients with OHSS. Our study outcome was any hospitalization for acute ischemic stroke, acute myocardial infarction, cerebral venous sinus thrombosis, pulmonary embolism, or acute deep venous thrombosis during the index hospitalization or within 90 days of OHSS diagnosis. Results and conclusionsWe found very few major ischemic events in patients with OHSS.

The effect of intravenous calcium gluconate on the prevention of ovarian hyperstimulation syndrome. (A randomized clinical trial)

ObjectiveOral Cabergoline and intravenous Calcium have the potential to prevent Ovarian Hyperstimulation Syndrome (OHSS) in assisted reproductive technology by regulating the activity of the Vascular Endothelial Growth Factor (VEGF) receptor. The purpose of this study was to examine the effect of Cabergoline with intravenous Calcium versus oral Cabergoline alone on the overall rate of OHSS. MethodsThis study is a randomized clinical trial which was carried out in Milad Infertility Center affiliated with Mashhad University of Medical Sciences, Mashhad, Iran between April 2016 and January 2018. A total of 192 patients were randomly assigned into two groups. The control group received oral Cabergoline and the intervention group received Calcium gluconate in addition to Cabergoline. A total rate of OHSS, moderate and severe OHSS were measured in both groups. ResultsThe demographic characteristics of the participants and the types of drugs used showed homogeneity between the intervention and control groups (P > 0.05). Furthermore, there was no significant difference between the two groups in terms of the number of the follicle, oocytes obtained, metaphase II oocytes, the number of embryos, and the rate of fertilization. Regarding the incidence of OHSS, 26.2 % of participants in the control group experienced OHSS, while the occurrence rate was 15.7 % in the intervention group (P = 0.401). The incidence of severe OHSS in the control group and intervention group was 7.1 % and 3.6 %, respectively. ConclusionIntravenous injection of Calcium gluconate can be effective in preventing Ovarian Hyperstimulation Syndrome.

Oocyte yield and live birth rate after follitropin delta dosing and fresh embryo transfer: an individual patient data meta-analysis

Research questionWhat number of retrieved oocytes is associated with the optimum chance to achieve a live birth for women undergoing ovarian stimulation with individualised follitropin delta? DesignIndividual patient data meta-analysis of 1772 patients from five randomised controlled trials using individualised follitropin delta for ovarian stimulation with fixed daily dosing based on serum anti-Müllerian hormone (AMH) and body weight. Outcomes of live birth rate (LBR) and ovarian hyperstimulation syndrome (OHSS) were evaluated in relation to the number of oocytes retrieved, including subgroup analyses based on number of oocytes retrieved, age and AMH levels. ResultsThe analysis included patients treated with follitropin delta who had ≥1 oocyte retrieved. The mean number of oocytes retrieved was 10.4 and the overall LBR was 32.1%. Predicted LBR increased with the number of oocytes retrieved, reaching above 34% in the range 8-14 oocytes, peaking at 34.9% for 11 oocytes. Beyond 14 oocytes, LBR gradually declined. By number of oocytes retrieved (grouped), the LBR was 27.8%, 33.6% and 30.9% at 1-7, 8-14 and ≥15 oocytes, respectively. LBR decreased with increasing age (32.7%, 30.7% and 23.4% at <35, 35-37 and 38-42 years, respectively). The incidence of OHSS (any grade) increased from 2.1% to 5.2% to 17.0% at 1-7, 8-14 and ≥15 oocytes retrieved. ConclusionsAfter ovarian stimulation with individualised follitropin delta, the LBR in the fresh cycle was highest in the range of 8-14 oocytes retrieved, peaking at 11 oocytes. The results support the appropriateness of the follitropin delta dosing algorithm.

Ovarian Hyperstimulation Syndrome (OHSS): A Narrative Review and Legal Implications.

Infertility is a highly meaningful issue with potentially life-changing consequences, and its incidence has been growing worldwide. Assisted reproductive technology (ART) has made giant strides in terms of treating many infertility conditions, despite the risk of developing ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication. This narrative review draws upon scientific articles found in the PubMed database. The search spanned the 1990-2024 period. Search strings used included "OHSS" or "ovarian hyperstimulation" and "IVF" and "GnRH" and "hCG"; 1098 results were retrieved and were ultimately narrowed down to 111 suitable sources, i.e., relevant articles dealing with the condition's underlying dynamics, management pathways, and evidence-based criteria and guidelines, crucial both from a clinical perspective and from the standpoint of medicolegal tenability. The following features constitute OHSS risk factors: young age, low body weight, and polycystic ovarian syndrome (PCOS), among others. GnRH antagonist can substantially lower the risk of severe OHSS, compared to the long protocol with a gonadotropin-releasing hormone (GnRH) agonist. However, a mild or moderate form of OHSS is also possible if the antagonist protocol is used, especially when hCG is used for the final maturation of oocytes. For women at risk of OHSS, GnRH agonist trigger and the freeze-all strategy is advisable. OHSS is one of the most frequent complications, with a 30% rate in IVF cycles. Providing effective care for OHSS patients begins with early diagnosis, while also evaluating for comorbidities and complications. In addition to that, we should pay more attention to the psychological component of this complication and of infertility as a whole. Compliance with guidelines and evidence-based best practices is essential for medicolegal tenability.

Effect of baseline LH/FSH ratio in PCOS on IVF-ET outcomes: a retrospective cohort study

Objective: To exlplore the association between the baseline luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio of polycystic ovary syndrome (PCOS) and in vitro fertilisation-embryo transfer outcomes. Methods: This was a retrospective cohort study. A total of 2 868 PCOS patients were enrolled, all of the participants were patients in The First Affiliated Hospital of Anhui Medical University Hospital from October 2015 to October 2021. Propensity score matching (1∶2.5) was conducted to regulate the non-random allocation of patients. Data were extracted from the hospital's medical records. Patients with baseline LH/FSH ratio>2 were deemed as study group, patients with baseline LH/FSH ratio≤2 were deemed as control group. Single factor analysis was applied to compare the differences of pregnancy outcomes between two groups. Results: After propensity score matching (1∶2.5), there were no statistically significant differences in baseline data between the two groups (all P>0.05), indicating that the data were comparable. In the study group, the total dose of gonadotropin (Gn) and duration of Gn were lower than those of the control group (t=4.989, P<0.001; t=3.267, P=0.001), the rate of in vitro maturation was higher than that of the control group (χ2=4.938, P=0.026), the number of retrieved oocytes and cleavage were higher than those of the control group (t=-2.305, P=0.021; t=-2.816, P=0.005), but there were no differences in the number and rate of high-quality embryos between the two groups (t=-1.636, P=0.102; t=-0.123, P=0.902). The incidence of moderate to severe ovarian hyperstimulation syndrome in the study group was significantly higher than that in the control group (χ2=17.277, P<0.001). Regardless of fresh embryo transfer or frozen-thawed embryo transfer cycles, the incidences of gestational diabetes mellitus in the study group were higher than those in the control group (χ2=9.174, P=0.002; χ2=4.204, P=0.040) of singleton pregnancy. In the fresh embryo transfer cycle, the clinical pregnancy rate [30.30% (20/66) vs 47.75% (53/111)] and delivery rate [30.30% (20/66) vs 46.85% (52/111)] in the study group were lower than those in the control group (χ2=5.198, P=0.023; χ2=4.695, P=0.030). In the frozen-thawed embryo transfer cycle, the delivery rate in the study group was higer than that in the control group [59.41% (423/712) vs 55.04% (1 053/1 913); χ2=7.526, P=0.023]. The clinical pregnancy rate and delivery rate of fresh embryo transfer cycle in the study group were significantly lower than those of frozen-thawed embryo transfer cycle (χ2=21.308, P<0.001; χ2=20.871, P<0.001), but there were no significant differences in the control group (all P>0.05). Conclusions: PCOS patients with a higher basal LH/FSH ratio are more likely to develop moderate to severe ovarian hyperstimulation syndrome after controlled ovarian stimulation and have a higher incidence of gestational diabetes mellitus. Better pregnancy outcome could be obtained by frozen-thawed embryo transfer.

Comparing risk factors and neonatal outcomes in women with intrahepatic cholestasis of pregnancy between assisted reproductive technology and spontaneous conception.

The aim of the present study was to investigate the incidence of intrahepatic cholestasis of pregnancy (ICP) as well as neonatal outcomes between conception via invitro fertilization (IVF) compared with spontaneous conception (SC) and screen the risk factors of ICP in IVF. This retrospective cohort study included 4467 puerperae who conceived via IVF, and 28 336 puerperae who conceived spontaneously and linked the information from neonates. The general linear model (GLM), multivariate logistic regression analysis, a forest plot, and nomogram were used to assess impact factors and risk prediction. Logistic analysis adjusted for confounders revealed significant differences in the ICP rate of singleton delivery (4.24% vs 3.41%, adjusted OR [aOR] = 1.26; 95% confidence interval [CI] 1.03-1.53, P = 0.025) and in groups with total bile acids (TBA) ≥40 and <100 μmol/L (14.77% vs 10.39%, aOR = 1.31; 95% CI: 1.06-1.63, P = 0.023) between IVF and SC. When we divided newborns into singleton and twins delivery, the GLM revealed a higher rate with Apgar score <7 (13.44% vs 3.87%, aOR = 3.85; 95% CI: 2.07-7.17, P < 0.001) and fetal distress for IVF in comparison with SC (19.32% vs 5.55%, OR = 3.48; 95% CI: 2.39-6.95, P < 0.001) in the singleton group. In multivariate logistic regression analysis, body mass index (BMI) (aOR = 1.29; P = 0.031), number of embryo transfers (ET) (single ET vs double ET, aOR = 2.82; P < 0.001), E2 level on the ET day (aOR = 2.79; P = 0.011), fresh ET which compared with frozen ET (FET) (aOR = 1.45; P = 0.014), embryo stage (cleavage embryo vs blastocyst, aOR = 1.75; P = 0.009) and severe ovarian hyperstimulation syndrome (OHSS) which compared with non-OHSS (aOR = 3.73; P = 0.006) were independent predictors of ICP. These predictive factors in the logistic regression model were integrated into the nomogram (C-index = 0.735; 95% CI: 0.702-0.764); for each patient, higher total points indicated a higher risk of ICP. We observed that the ICP rate of singleton delivery was higher in IVF than in SC. In ICP patients, there were higher rates of neonatal Apgar score <7 and fetal distress in IVF than SC and found the predictors of ICP in IVF.

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

Competence of Combined Low Dose of Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate (CC) Versus Continued CC during Ovulation Induction in Women with CC-Resistant Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.

Causal relationship between OHSS and immune cells: A Mendelian randomization study

ObjectiveTo confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. DesignObtaining data, collecting single nucleotide polymorphisms, detecting instrumental variables heterogeneity, assessing causality, and assessing bidirectional causality. SubjectsA two sample Mendelian study to confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. ExposureImmune cell phenotype (including 22 million SNPs from GWAS on 3757 European individuals). Main outcome measuresInverse variance weighting, one-sample analysis, MR-Egger, weighted median and weighted mode are used to assess the causal relationship between 731 immunophenotypes and Ovarian Hyperstimulation Syndrome. The weighted median and Mendelian Randomization multi-effect residuals and Mendelian Randomization multi-effect residuals and outlier tests are used to assess bidirectional causality between this two. ResultsAfter False Discovery Rate correction, 9 immunophenotypes were found to be significantly associated with the risk of Ovarian Hyperstimulation Syndrome. B cell panel: IgD+ AC (OR, 0.90) 、CD19 on CD24+ CD27+ (OR, 0.86) 、BAFF-R on CD20- CD38 (OR, −1.22); Mature T cell group panel: EM DN (CD4 -CD8-) AC (OR, 1.46); Myeloid cell panel: Mo MDSC AC (OR, 1.13) 、CD45 on CD33br HLA-DR+ (OR, 0.87); Monocyte panel: HLA-DR on monocyte (OR, 0.86) 、CCR2 on CD14+ CD16+ monocyte (OR, 1.15) 、cDC panel: HLA-DR on myeloid DC (OR, 0.89). ConclusionThis study shows the potential link between OHSS and immune cells by genetic means, providing new ideas for future clinical and basic research.

Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

Impact of Luteinizing Hormone on IVF/ICSI Assisted Reproduction on the Initiation Day of Gonadotropin-releasing Hormone Antagonist Protocol.

The aim of the study was to explore the optimal timing of gonadotropin initiation and the reasonable interval of luteinizing hormone (LH) levels in the gonadotropin-releasing hormone antagonist (GnRH-A) protocol. A retrospective cohort study was conducted to analyze the data concerning the oocyte retrieval cycles from 1,361 cases with the GnRH-A protocol implemented. The ovarian responses (including AMH, AFC) in these patients were divided into the poor ovarian response group (an antral follicle count [AFC] ≤ 6, n = 394), the normal ovarian response group (an AFC > 6 and < 15, n = 570), and the high ovarian response group (an AFC ≥ 15, n = 397), according to the AFC. The patients were sub-grouped according to LH levels on the protocol initiation day, and the clinical outcomes (including dose of Gn initiation, Gn administration days, GnRH-ant administration days, P levels on the HCG day, E2 levels on the HCG day, LH levels on the HCG day, number of embryos transferred, total fertilization rate, embryo implantation rate(%), proportion of 2PN, proportion of good-quality embryos, endometrial thickness on the hCG injection day(mm), moderate to severe OHSS, AFC on the initiation day, proportion of type A endometrium on the hCG injection day, clinical pregnancy rate, biochemical pregnancy rate, early abortion rate, ectopic pregnancy rate) were compared. On the GnRH-A protocol initiation day, among all patients with different ovarian responses, the body mass index (BMI) in those with an LH ≥ 5 IU/L was lower. The differences in pregnancy outcomes between the LH < 5 IU/L group and the LH ≥ 5 IU/L group were not statistically significant across the different ovarian response groups, but the LH < 5 IU/L group had a higher proportion of good-quality embryos (80.3±24.9 vs. 74.8±26.9, P =0.035) than the LH≥5IU/Lgroup in those with poor ovarian response. The total fertilization rate (82.2±18.1 vs 85.4±15.1, P =0.021) and proportion of two pronuclei (2PN) (69.0±20.9 vs 72.7±19.9, P =0.035) were higher in the LH ≥ 5 IU/L group than the LH<5 IU/L group for those with normal ovarian responses. The embryo implantation rate (41.4±41.3 vs 52.6±43.4, P =0.012) was higher in the LH ≥ 5 IU/L group than in the LH<5 IU/L group in those with high ovarian response. The results of the multivariate logistic analysis showed that the age of the female partner, number of embryos transferred, proportion of good-quality embryos, endometrial thickness on the hCG injection day, and moderate- to-severe ovarian hyperstimulation syndrome (OHSS) were independent factors correlated with the outcome of live births (P < 0.05). The LH levels on the gonadotropins (Gn) initiation day in the GnRH-A protocol will not affect pregnancy outcomes.

Ovarian hyperstimulation syndrome: an overview and prevention approaches

Ovarian hyperstimulation syndrome: an overview and prevention approaches