The Fluid Wave of Fertility: A Case of Ovarian Hyperstimulation Syndrome in a Lung Transplant Patient

Y.A. Bassiouny, D.M.R. Dakhly, Y.A. Bayoumi, N.A. Salaheldin, H.A. Gouda, and A.A. Hassan, "Randomized Trial of Combined Cabergoline And Coasting in Preventing Ovarian Hyperstimulation Syndrome During InVitro Fertilization/intracytoplasmic Sperm Injection Cycles," International Journal of Gynecology & Obstetrics 140, no. 2 (2018): 217-222, https://doi.org/10.1002/ijgo.12360. This retraction has been issued for the above article, published online on 21 October 2017 in Wiley Online Library (wileyonlinelibrary.com), by agreement between the journal Editor-in-Chief, Michael Geary; and John Wiley & Sons Ltd. A third party expressed concerns about the randomization allocation process, noting that the reported methodology does not appear to reflect the standards of a randomized clinical trial. When asked for clarification, the authors provided their study data and explanation. However, the editorial team and publisher did not feel that the answers and data alleviated the concerns with the methodology. While the work may have been undertaken in good faith, it does not meet the minimum standards to constitute a randomized study. As a result, the data and conclusions are considered unreliable, and therefore the article must be retracted.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and a major cause of anovulatory infertility, often requiring assisted reproductive technology (ART). The freeze-all strategy followed by frozen-thawed embryo transfer (FET) can reduce the risk of ovarian hyperstimulation syndrome (OHSS) and improve endometrial receptivity. However, women with PCOS still experience suboptimal reproductive outcomes. Increasing evidence suggests that chronic low-grade inflammation may contribute to these impairments. Conventional inflammatory markers, such as circulating cytokines, are not routinely assessed in clinical practice, underscoring the need for simple and accessible indicators. Recently, several hematologic and lipid-based inflammatory ratios-lymphocyte-to-HDL cholesterol ratio (LHR), neutrophil-to-HDL cholesterol ratio (NHR), platelet-to-HDL cholesterol ratio (PHR) and monocyte-to-HDL cholesterol ratio (MHR)-have been proposed as accessible indicators of systemic inflammation. Nevertheless, their predictive value for ART outcomes in women with PCOS remains unclear. This retrospective cohort study included 1445 women with PCOS undergoing their first frozen embryo transfer cycle at the reproductive medicine center of a tertiary hospital between 2010 and 2023. The associations of reproductive outcomes with NHR, LHR, PHR and MHR were assessed using logistic regression models with or without adjusting for potential confounders. Higher quartiles of NHR, LHR, and PHR were associated with increased miscarriage rates and decreased live birth rates, whereas no consistent pattern was observed for MHR. No significant differences were found across quartiles in biochemical pregnancy, clinical pregnancy, preterm delivery and low birth weight. Compared with women in the lowest quartile, those in the highest quartile had significantly higher odds of miscarriage for NHR (adjusted odds ratio [OR] 2.51, 95% confidence interval [CI] 1.39-4.63), LHR (2.32, 1.23-4.49) and PHR (2.47, 1.34-4.64). In addition, LHR and PHR were inversely associated with live birth after full adjustment. Elevated NHR, LHR, and PHR were associated with adverse reproductive outcomes in women with PCOS undergoing FET. These findings suggest that HDL-C related inflammatory ratios may have potential value as accessible markers of systemic inflammation in this population. However, given the retrospective design, their clinical utility for risk stratification and individualized management requires further validation in prospective studies. Not applicable.

BackgroundOvarian hyperstimulation syndrome (OHSS) is a severe iatrogenic disorder resulting from controlled ovarian stimulation. The administration of a gonadotropin-releasing hormone antagonist (cetrorelix) during the luteal phase is a practical approach for preventing OHSS.ObjectiveThis study aimed to evaluate the efficacy and safety of different cetrorelix regimens for preventing OHSS in high-risk groups.Materials and Methods In this cross-sectional study, data of 271 women with a high-risk profile for OHSS presented to the Infertility Center of Kosar hospital, Urmia, Iran from March 2023 and March 2025 and those who underwent intracytoplasmic sperm injection were extracted from their medical records. Participants were given prophylactic luteal-phase cetrorelix regimen of 0.5 mg twice daily (BID group, n = 101), 0.5 mg 3 times daily (TDS group, n = 38), or 0.75 mg TDS group (n = 102). After correcting for baseline characteristics, a logistic regression model determined independent hospitalization predictors. The primary outcomes measured in this study were the frequency and severity of OHSS and the rate of hospitalization due to OHSS. OHSS severity was graded according to standard classification, and hospitalization was defined as the need for inpatient management of OHSS. The study then compared these outcomes across the 3 different cetrorelix dosing regimens.ResultsOHSS frequency and severity decreased in a dose-dependent way, with no moderate or severe cases in the 0.75 mg TDS group (p 0.001). Lower-dose groups had higher hospitalization rates than the 0.75 mg TDS reference group after adjusting for confounding variables. The likelihood was 20 times higher for the 0.5 mg TDS group (adjusted odds ratio = 19.92, 95% CI [1.99, 199.04]) and 79 times higher for the 0.5 mg BID group (adjusted odds ratio = 79.29, 95% CI [9.31, 675.43]).Conclusion In individuals with elevated risk, 0.75 mg TDS luteal-phase cetrorelix more effectively decreases OHSS risk and reduces hospitalizations compared to lower dosages.

Serum PFAS mixtures and risk of ovarian hyperstimulation syndrome in women undergoing assisted reproduction.

Human menopausal gonadotrophin in a pre-filled injection pen is non-inferior to the US-approved powder formulation.

The article "Use of Intramuscular Progesterone versus Intravenous Albumin for the Prevention of Ovarian Hyperstimulation Syndrome" [Gynecol Obstet Invest. 2000;50(3):182-185; https://doi.org/10.1159/000010306] by Loredana Costabile, Vittorio Unfer, Claudio Manna, Sandro Gerli, Dario Rossetti and Gian Carlo Di Renzo has been retracted by the Publisher and the Editors.After publication of this article, concerns were raised about the uneven group sizes following randomization, the reported rate of pregnancy following transfer, which was higher than described in contemporary global statistics, and the significant difference between groups in the number of oocytes retrieved, though the differential intervention occurred post-retrieval. These raised concerns about the study's randomization. When asked to comment, the authors stated that they cannot address the concerns due to the fact that the article was published more than 25 years ago and data and documents are no longer available.The concerns raised and the authors' response were reviewed by the Editors. As the concerns, which may impact the reliability of findings presented in the article, cannot be addressed or resolved, and due to the relevance of the difference between the groups for the conclusions of the study, the article is being retracted.Vittorio Unfer does not agree to the retraction. Sandro Gerli stated that he bears no responsibility for this article. The remaining authors did not respond to the notification about this retraction within the timeframe specified.

Clinical outcomes of combining recombinant follicle-stimulating hormone (rFSH) with highly purified human menopausal gonadotropin (HP-hMG) versus rFSH alone were compared in patients undergoing in vitro fertilization in a real-world setting. This retrospective cohort study analyzed patients who underwent ovarian stimulation with rFSH or rFSH + HP-hMG following a gonadotropin-releasing hormone antagonist protocol, followed by fresh or frozen embryo transfer (ET) at two centers in Korea. A total of 1,028 women were included: 329 underwent fresh ET (rFSH: n = 78; rFSH + HP-hMG: n = 251) and 699 underwent frozen ET (rFSH: n = 250; rFSH + HP-hMG: n = 449). Across both fresh and frozen ET group, patients receiving rFSH + HP-hMG were older and had lower anti-Müllerian hormone levels and antral follicle counts. Despite fewer oocytes retrieved in rFSH + HP-hMG group (fresh: 9.5 vs. 11.0; frozen: 16.3 vs. 20.6, both p < 0.05), metaphase II oocyte rates and clinical pregnancy rates were comparable (fresh: 44.6 vs. 43.6%; frozen: 58.4 vs. 56.8%, both p > 0.05). Notably, ovarian hyperstimulation syndrome incidence was significantly lower in rFSH + HP-hMG group among frozen ET patients (6.9 vs. 13.2%, p < 0.01). These findings suggest that rFSH + HP-hMG achieves comparable clinical outcomes to rFSH alone despite less favorable prognostic characteristics that could affect clinical outcome, supporting its role as a clinically acceptable alternative stimulation option in routine practice.

ABSTRACTPulmonary arterial hypertension (PAH) carries a high risk of maternal morbidity and mortality in pregnancy, and current guidelines advise against conception. For women with PAH who wish to have genetically related children, in vitro fertilisation (IVF) combined with gestational surrogacy presents a viable and increasingly safe alternative. Advances in IVF protocols—including gonadotropin‐releasing hormone (GnRH) antagonist stimulation, agonist trigger, personalised gonadotropin dosing, and elective embryo cryopreservation—have markedly reduced the risks of ovarian hyperstimulation syndrome and made oocyte retrieval feasible even in high‐risk populations. The addition of pre‐implantation genetic testing for monogenic disorders (PGT‐M) enables the selection of embryos free of heritable PAH‐related mutations, while pre‐implantation genetic testing for aneuploidy (PGT‐A) improves implantation rates and reduces miscarriage. For women who, due to personal, cultural or legal reasons, decline surrogacy and choose to carry a pregnancy themselves, a conservative approach—using natural cycle frozen embryo transfer and single euploid embryos—can reduce, but not eliminate, risk. The risks of pregnancy in this population are acknowledged to be high, and the guidelines continue to mandate against PAH patients becoming pregnant. However, there are alternative strategies developing which may allow biological parenthood without some of the inherent cardiopulmonary risk. This paper reviews the available evidence and proposes a clinical framework for offering IVF safely in this population, while advocating for the development of a dedicated registry and expert consensus to guide future care.

Spontaneous ovarian hyperstimulation syndrome (OHSS) is closely associated with follicle stimulating hormone receptor (FSHR)functional mutations. We observed that estrildid finches naturally carry the gain-of-function FSHR p.Thr449Ala mutation found in humans, yet do not develop OHSS, thereby providing a novel and system to study aspects of OHSS prevention. Cross-species single-cell analysis revealed that macrophages, the most abundant immune cells in ovaries, play a pivotal role in OHSS progression. Macrophage depletion exacerbates the manifestations of OHSS in both birds and rats. Pharmacological activation of the G protein-coupled receptor 183 (GPR183) in ovarian macrophages, significantly alleviates OHSS symptoms. Mechanistically, GPR183 activation in macrophages maintains ovarian immune homeostasis by downregulating inflammatory factors (Interleukin 1 alpha: IL1A, Interleukin 6: IL6, Interleukin 1 beta: IL1B) and upregulating immune regulators responsive to external stimuli (sphingomyelin phosphodiesterase acid like 3A: Smpdl3a, Macrophage-expressed gene 1: Mpeg1, Epithelial stromal interaction 1: Epsti1, Unc-93 homolog B1: Unc93b1, Apolipoprotein B mRNA editing enzyme catalytic subunit 1:Apobec1). It markedly altered CD44 molecule (CD44)/Syndecan-4 (SDC4) -mediated intercellular communication between macrophages and endothelial/stromal cells, thereby modulating the ovarian microenvironment. This study identifies ovarian macrophages as a key therapeutic target for OHSS and proposes GPR183 as a novel receptor target for precision macrophage-based interventions.

Ovarian hyperstimulation syndrome is a potentially serious complication of fertility treatments. Standard care often involves monitoring, then hospitalisation for severe cases. Some evidence suggests early outpatient paracentesis may prevent hospitalisation, but adequately powered randomised trials are lacking. To establish the clinical and cost-effectiveness, safety and acceptability of early active outpatient management for moderate or severe ovarian hyperstimulation syndrome. A pragmatic, parallel, open-label, multicentre, superiority, adaptive, group sequential randomised controlled trial with an internal pilot was planned. The study included preliminary qualitative work and a post-trial survey. The main trial recruited participants with moderate or severe, early or late ovarian hyperstimulation syndrome from UK fertility clinics. Participants were randomised 1 : 1 to receive either outpatient paracentesis or usual care (conservative management). The primary outcome was ovarian hyperstimulation syndrome-related hospital admission within 28 days. The trial was terminated early due to poor recruitment. Only 8 participants were randomised (5 to conservative management, 3 to outpatient paracentesis) across 3 of 9 opened sites, compared to the planned 224 participants. All eight had moderate ovarian hyperstimulation syndrome at baseline. Two participants were hospitalised for ovarian hyperstimulation syndrome-related reasons (one from each group). Six participants' symptoms resolved during follow-up, while two had unknown outcomes. There were no reported serious adverse events caused by the intervention. The post-trial survey of 16 fertility centres found increased use of preventive measures like freeze-all cycles, antagonist protocols and gonadotropin-releasing hormone trigger, during and after the SARS-CoV-2 (COVID-19) pandemic. The small sample size precludes drawing any definitive conclusions about effectiveness, safety or cost-effectiveness. The study was severely impacted by the COVID-19 pandemic, affecting site set-up and recruitment, and changes in clinical practice during the pandemic may have reduced ovarian hyperstimulation syndrome cases. No definitive clinical conclusions can be drawn from this study about the effectiveness of outpatient management compared to conservative management. The pandemic prompted lasting modifications in ovarian hyperstimulation syndrome prevention strategies at many fertility clinics. Given the observed low incidence rates of ovarian hyperstimulation syndrome and challenges in recruitment, future research may need to consider alternative study designs in observational settings rather than randomised trials that reflect the changing reality of clinical management and prevention of ovarian hyperstimulation syndrome, particularly following the recent COVID pandemic. Additionally, the research community should reflect on strategies to improve trial resilience and adaptability in the face of major disruptions like pandemics. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128137.

This study aimed to conduct computer searches in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, VIP, Wanfang, and CBM databases. Literature was screened and data extracted according to the inclusion and exclusion criteria. RevMan 5.3 was used to assess the methodological quality of the included studies, while Stata 14.0 was employed to rank the efficacy and safety of the five interventions. This analysis included 20 randomised controlled trials involving a total of 2,400 patients. The cumulative probability ranking results showed that, for improving clinical pregnancy rate (CPR), leuprorelin (97.8%) ranked highest, followed by cetrorelix (70.7%), triptorelin (47.9%), buserelin (18.2%), and ganirelix (15.3%). For improving the live birth rate (LBR), leuprorelin (99.9%) ranked highest, followed by triptorelin (44.1%) and cetrorelix (5.9%). For reducing the incidence of ovarian hyperstimulation syndrome (OHSS), cetrorelix (96.9%) ranked highest, followed by buserelin (58.7%), ganirelix (57.5%), leuprorelin (21.2%), and triptorelin (15.7%). Cetrorelix demonstrated superior performance in reducing the risk of OHSS, while leuprorelin was more effective in improving CPR and LBR. For women with polycystic ovary syndrome at high risk of OHSS, cetrorelix is recommended. For patients with the primary goal of improving CPR or LBR, leuprorelin is the more appropriate choice. Key Words: Polycystic ovary syndrome, Infertility, GnRH agonist, GnRH antagonist, Assisted reproduction.

Background: Egg donation as an aspect of assisted reproductive technology has brought hope to several individuals and couples with various forms of infertility. Whereas literature from around the globe has been rich on its ethical, psycho-social, and health dimensions, Sub-Saharan Africa has remained underrepresented in that discourse. This review, therefore, synthesizes international evidence and contextualizes it for Sub-Saharan African settings. This is despite the fact that there are significant research gaps, particularly on the health outcomes of donors over the longer term, investigation of psychosocial effects, and understanding of how different compensation and consent frameworks affect the experiences of donors. Most importantly, empirical studies from Sub-Saharan Africa remain scant, with a lack of culturally adapted ethical guidelines. Methodology: The study used PRISMA guidelines to comprehensively search the databases: Medline/PubMed, EMBASE, Wiley Cochrane, and Clinicaltrials.gov. Studies in the form of surveys, systematic reviews, and qualitative interviews were analyzed using a narrative synthesis approach. A total of 5528 papers as of October 2nd, 2025, were reviewed, out of which only 14 papers were selected since they fit into the criteria. The Newcastle-Ottawa scale was used for quality assessment. Results: Informed consent procedures often lack the presence of long-term risks, and compensation practices are highly variable, with the potential for exploitation. Donors report a range of psychosocial outcomes from altruism to identity-related distress. Health risks include ovarian hyperstimulation syndrome, although the possible links with breast and ovarian cancers are not established due to limited long-term data. Conclusions: The implications are equally clear: ethical egg donation in Sub-Saharan Africa should be based on consent models sensitive to culture, regulated compensation frameworks, and mandated counseling protocols. Registries of don

Luteinizing hormone (LH) activity plays a crucial role in follicular development, endometrial decidualization, and embryo implantation. We aimed to compare the efficacy and safety of gonadotropins with LH activity versus recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation (COS). We included randomized clinical trials (RCTs) assessing gonadotropins with LH activity with or without rFSH versus rFSH, or comparing different sources of LH activity, or different doses. Participants were women undergoing COS. The outcomes were live births, ongoing pregnancies, oocytes recovered per woman, metaphase II (MII) oocytes per woman, and occurrence of ovarian hyperstimulation syndrome (OHSS). We searched the MEDLINE, Embase, and CENTRAL databases. We calculated the mean differences (MDs) and risk ratios (RRs) for continuous and dichotomous outcomes, respectively. We included 56 RCTs with 14,034 women. The evidence of gonadotropins with LH activity (±rFSH) when compared with rFSH alone probably results in little to no difference in live birth (RR=1.07, 95%CI = 0.96-1.18; 17 studies, moderate certainty of evidence) and ongoing pregnancy (RR=1.03, 95%CI = 0.95-1.12; 19 studies, moderate certainty of evidence), may result in a slight reduction in the number of oocytes retrieved (MD = -0.50, 95%CI = -0.88 to -0.12, I 2 = 81.1%; 46 studies, low certainty of evidence), and is very uncertain in the number of MII oocytes (MD = -0.49, 95%CI = -0.93 to -0.05, I 2=86%; 30 studies, very low certainty of evidence). However, it probably does not increase OHSS compared with rFSH alone (RR=0.80, 95%CI = 0.61-1.03, I 2=17.1%; 19 studies, moderate certainty of evidence). Subgroup analysis by downregulation protocol, ovarian reserve, and age showed some differences in the effects between the compared groups. The evidence of gonadotropins with LH activity (±rFSH) when compared with rFSH alone probably results in little to no difference in live birth and ongoing pregnancy. However, there is a slight reduction in the number of oocytes retrieved. Moreover, they are safer than rFSH alone because they probably do not increase OHSS. Therefore, based on our review, the benefit-risk balance favors the addition of an LH-active gonadotropin for the prevention of OHSS. More studies are needed to determine the effects in specific populations. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024572731, identifier CRD42024572731.

Effects of human umbilical cord derived mesenchymal stem cells transplantation on ovarian function in rats with ovarian hyperstimulation syndrome.

To compare the frequency of ovarian hyperstimulation syndrome in infertile females with GnRH agonists versus GnRH antagonists seeking invitro fertilization Study design A prospective cohort study Settings and duration At Obstetrics and Gynecology Department of Hameed Latif Hospital, Lahore,from 4th January 2024 to 4th January 2025 Methods A total of 60 infertile women aged 20-40 years referred for the first IVF/ ICSI were selected for the study, using non-probability, consecutive sampling.Women were divided into two groups: Group A and Group B. Patients in Group A were 30 women administered 500 µg GnRH agonist (Buserelin) subcutaneously every day since the 21st day of the menstrual cycle. The dose was reduced by 300 µg on the 2nd day of the cycle after pituitary suppression, and 150 µg gonadotropin was added to the regimen. Patients in Group B were 30 women administered 0.25 mg GnRH antagonist (Cetrotide) subcutaneously. 150 IU Pregonal was administered intramuscularly from the third day.After ovum retrieval,if more than three follicles had estradiol greater than 3000 pg/ml at 3 months and 6 months, it was described as OHSS, which was managed by standard procedure Results The frequency of primary infertility patients in Group A was 16 (53.3%), and secondary infertility was 14(46.7%). The frequency of primary infertility patients in GroupB was 19(63.3%), and secondary infertility was 11(36.7%). The mean number of mature follicles of patients in GroupA was 14.4±1.27 (1-35). The mean number of mature follicles of patients in GroupB was 13.6±1.24 (2-27). The mean E2 level in patients of GroupA was 3261.8±134.7 (Range: 1008-4215) and the mean E2 level in patients of GroupB was 3500±167.4 (Range: 1000-4890). The frequency of patients with ovarian hyperstimulation syndrome in GroupA was 2 (6.7%) and in GroupB was 8 (26.7%). Conclusion GnRH agonist is more effective than GnRH antagonist in terms of frequency of ovarian hyperstimulation syndrome in infertile women seeking invitro fertilization.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder and a leading cause of anovulatory infertility. This study evaluated whether adding vitamin E to a regimen of letrozole, tamoxifen, and estradiol improves ovulation outcomes in infertile women with PCOS. In a double-blind, randomized clinical trial conducted in Jahrom, Iran (December 2023-August 2024), 90 infertile women with PCOS were randomly assigned to two groups. Group A (n=45) received letrozole, tamoxifen, estradiol, and vitamin E, while group B (n=45) received the same regimen without vitamin E. The primary outcome was pregnancy rate; secondary outcomes included follicle size, count, and endometrial thickness, measured on cycle days 3, 7, and 12. Data were analyzed using Chi-square, Fisher's exact, and t tests (Stata 14). Baseline characteristics including age (mean: 31.21 ± 6.31 Y), BMI (24.96 ± 3.45 kg/m²), and infertility duration (3.48 ± 2.70 Y) were similar between groups (P>0.05). On day 7, the vitamin E group showed significantly larger follicles (14.15 ± 0.36 mm vs. 10.90 ± 0.68 mm), more follicles (5.16 ± 0.36 vs. 3.73 ± 0.83), and thicker endometrium (7.16 ± 0.36 mm vs. 5.16 ± 0.36 mm). These advantages persisted on day 12, including improved follicular maturity and endometrial thickness. Although the pregnancy rate was higher in the vitamin E group (11.1% vs. 6.7%), the difference was not statistically significant (P=0.457). Adverse effects, including ovarian hyperstimulation syndrome (OHSS) and irregular bleeding, did not differ significantly (P=0.553). The results indicate that the addition of vitamin E to the letrozole-tamoxifen-estradiol protocol might be associated with improved ovulatory outcomes in women with PCOS. Nevertheless, no significant effect on pregnancy rates was observed. These findings highlight the potential adjunctive role of vitamin E in ovulation induction among women with PCOS, although further large-scale randomized trials are needed to confirm its clinical relevance (number registration: IRCT20150407021653N20).

Effect of Assisted Reproductive Technologies in Women With Cardiovascular Disease.

Evaluation of weight change during ovarian stimulation treatment.

Gain-of-function mutations in the human follicle-stimulating hormone receptor (FSHR) cause spontaneous ovarian hyperstimulation syndrome (OHSS), a serious reproductive disorder. However, the molecular physiology and treatment options for OHSS remain elusive. Notably, estrildid finches naturally carry an FSHR variant (Thr449Ala) analogous to the pathogenic mutation in humans yet are resistant to OHSS. Here we show that this resistance stems from significantly reduced luteinizing hormone receptor expression in estrildid ovarian granulosa cells. Furthermore, treatment with the luteinizing hormone receptor antagonist alleviates OHSS symptoms in mouse models. Single-cell RNA transcriptomic reveals functional compensation of the two receptors to regulate estrogen production and vascular permeability, resembling the adaptive mechanisms observed in estrildid finches. Our study unravels the molecular mechanism underlying the physiological adaptation of estrildid ovaries to high FSHR constitutive activity and is a example of how the concept of Darwinian Medicine could be exploited to identify novel drug targets for ovarian hyperstimulation syndrome treatment.