Search Results (22)

The final trigger of oocyte maturation is a pivotal step in assisted reproductive technology (ART). Different molecules and protocols—including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonists (GnRHa), the dual trigger, the double trigger, and emerging agents such as kisspeptin—have been investigated to optimize oocyte competence, embryo development, and pregnancy outcomes while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). HCG remains the most widely used trigger, but its pharmacological profile is associated with a significant risk of OHSS. GnRHa has emerged as an alternative in antagonist cycles, abolishing the risk of severe OHSS but often requiring tailored luteal phase support. Several strategies, including hCG, GnRHa, and combined approaches, have shown improvements in specific outcomes such as the oocyte maturity (MII) rate, fertilization rate, embryo development parameters, and, in selected contexts, a reduction in OHSS risk. Kisspeptin represents a promising option; however, its use remains predominantly within the research setting, with clinical application still limited to early-phase or highly selected studies. Beyond the choice of molecule, the timing of trigger administration—adjusted to follicle size, estradiol concentrations, and progesterone levels—also influences oocyte competence and subsequent clinical outcomes. Triggering final oocyte maturation remains a multifaceted decision that should be individualized according to patient characteristics, ovarian response, and risk of OHSS. Although hCG remains the historical reference standard, accumulating but heterogeneous evidence suggests that GnRHa-based strategies, including dual-trigger protocols, may improve specific outcomes in selected patient subgroups. However, results across trials are inconsistent, particularly in poor responders, and any exposure to hCG maintains a residual risk of OHSS. Kisspeptin represents a promising but still experimental option, with current data largely limited to early-phase clinical studies in highly selected high-risk populations. Well-designed randomized trials are required to clarify the true impact of these strategies on live birth, to refine timing and dosing, and to better define which patients are most likely to benefit. Full article

Background/Objectives: A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed. Methods: We report a case involving a 31-year-old woman who had never been pregnant and with irregular menstrual cycles. An ultrasound scan performed on the second day of the cycle showed several annular follicles, a high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio suggesting polycystic ovary syndrome (PCOS), and an undetectable serum level of AMH. Results: Despite these observations, she exhibited an unpredictable hyperresponse during controlled ovarian stimulation, followed by a failed pregnancy despite successful in vitro fertilization with ICSI and a good-quality thawed embryo transfer (4AA). Conclusions: This case highlights the challenges of relying solely on AMH as a predictive marker of ovarian response. Although AMH is widely used for assessing ovarian reserve and stimulation outcomes, its limitations become evident in atypical cases. The paradoxical hyperresponse observed here may result from alternative regulatory mechanisms influenced by elevated LH levels, enhanced gonadotropin receptor sensitivity, or local ovarian factors. This report underscores the need for a personalized, multidimensional approach combining hormonal profiles, ultrasound assessments, and clinical history to optimize stimulation protocols and mitigate risks such as ovarian hyperstimulation syndrome (OHSS). Such tailored protocols are essential for managing patients with complex profiles, particularly those with undetectable AMH levels. Further research is needed to explore the mechanisms behind these atypical ovarian responses, including the roles of genetic polymorphisms, inflammatory markers, and environmental factors. This case demonstrates the importance of cautious interpretation of AMH results and emphasizes the value of comprehensive evaluations in assisted reproductive technologies. Full article

Background: Ovarian hyperstimulation syndrome (OHSS) remains a major complication during controlled ovarian stimulation, particularly in women with high estradiol levels. This study aimed to investigate whether bazedoxifene or fulvestrant could be effective in preventing OHSS. Methods: Forty 22-day-old Wistar albino rats were randomly assigned to four groups (n = 10 each). Group 1 received saline (negative control). Group 2 received pregnant mare serum gonadotropin (PMSG) plus hCG (positive control). Group 3 received PMSG + hCG plus fulvestrant, and Group 4 received PMSG + hCG plus bazedoxifene. Rat weight, peritoneal fluid, follicle counts, serum estradiol and VEGF levels, and ovarian ER/VEGF immunoreactivity were evaluated. Results: Peritoneal fluid was absent in controls but detected in 80% of positive controls and 40% of both treatment groups. Tertiary follicles and atresia were significantly higher in OHSS rats compared to controls. Fulvestrant reduced stromal ER expression, while bazedoxifene increased it. Both drugs decreased ascites formation and weight gain. Fulvestrant treatment showed unexpectedly elevated serum estradiol levels, likely due to assay interference. Conclusions: Fulvestrant and bazedoxifene may reduce OHSS severity by lowering ascites formation and weight gain. These agents could be potential therapeutic candidates for OHSS with appropriate timing and dosage. Full article

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Objectives: Our aim is to report an uncommon pituitary activation occurring during the desensitization phase of the gonadotropin-releasing hormone agonist (GnRHa) long protocol, a cornerstone of medically assisted reproduction (MAR) therapy, in a young woman. Results: We present a case of a 33-year-old female patient with secondary infertility, who exhibited a prolonged and asynchronous follicular development during ovarian stimulation using the GnRH antagonist protocol. Therefore, during a repeat attempt, the long GnRH agonist protocol was employed. Surprisingly, rather than achieving suppression with the agonist, ultrasound detected many large follicles in both ovaries, accompanied by extremely elevated estrogen levels, indicating imminent ovarian hyperstimulation syndrome (OHSS). This unusual phenomenon was also observed during a subsequent attempt using the long protocol in another reproductive center. As part of the work-up to identify the underlying etiology, contrast-enhanced magnetic resonance imaging (MRI) of the sella turcica was performed, which revealed an 11 × 13 × 10 mm pituitary macroadenoma without evidence of pathological hormone secretion. The luteinizing hormone-releasing hormone (LHRH) stimulation test showed a normal luteinizing hormone and follicle-stimulating hormone response. Other abnormalities of the hypothalamo–hypophyseal–target-organ axis were not found. Neurosurgical intervention was deemed unnecessary; radiological follow-up of the lesion was recommended. Conclusions: In this case, the clinical presentation was markedly different from the expected suppressive effects of GnRH agonist therapy, with profoundly elevated estrogen levels and clinical signs of imminent OHSS. Notably, hypersensitivity of the adenohypophysis was not demonstrated following a single physiological LHRH stimulation test. However, the presence of a pituitary adenoma identified on MRI raises the possibility that gonadotropin receptor function was altered by the lesion—an effect revealed only after repeated GnRH agonist exposure, resulting in a paradoxical stimulatory response. Full article

This narrative review summarizes the available literature on the association between In Vitro Fertilization (IVF) treatments and thrombosis, focusing on epidemiology and pathophysiology. Thrombosis is a rare IVF-related complication, with an incidence of approximately 0.2%, dramatically increased by ovarian hyperstimulation syndrome (OHSS). Arterial thrombosis, primarily associated with OHSS, is a rare and early event, while venous thrombosis, although more common, remains a rare complication of IVF. Venous thrombosis often affects the upper body. The thrombotic risk is higher during the first trimester of pregnancy obtained through IVF. This review discusses the impact of risk factors such as OHSS, thrombophilia, obesity, advanced maternal age, and polycystic ovarian syndrome, which predispose women to thromboembolic events during and after IVF stimulation. Full article

Background: 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. Methods: 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. Results: 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. Conclusion: 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. Full article

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease, usually presented in the third trimester with pruritus, elevated transaminase, and serum total bile acids. Evidence shows that it can be developed in the first trimester, more commonly after in vitro fertilization (IVF) procedures, with the presence of ovarian hyperstimulation syndrome (OHSS). Methods: A literature search was conducted in the PubMed/MEDLINE database of case reports/studies reporting early-onset ICP in spontaneous and IVF pregnancies published until July 2023. Results: Thirty articles on early-onset ICP were included in the review analysis, with 19 patients who developed ICP in spontaneous pregnancy and 15 patients who developed ICP in IVF pregnancies with or without OHSS. Cases of 1st and 2nd trimester ICP in terms of “early-onset” ICP were pooled to gather additional findings. Conclusions: Proper monitoring should be applied even before expected pregnancy and during IVF procedures in patients with known risk factors for OHSS and ICP development (patient and family history), with proper progesterone supplementation dosage and genetic testing in case of ICP recurrence. Full article

Thrombocytes play an essential role in hemostasis and thrombosis. Moreover, the controlled activation of thrombocytes is required in reproduction and fertility. The platelet-activating factor and the controlled activation of platelets have important roles in folliculogenesis, ovulation, placental development, implantation and embryo development. Activated platelets accumulate in the follicular vessels surrounding the follicle and, due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters), locally increase oocyte maturation and hormone secretion. Furthermore, activated platelets are involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) and preeclampsia. Low-dose aspirin can prevent OHSS during ovulation induction, while intrauterine or intraovarian administration of platelet-rich plasma (PRP) increases the endometrium thickness and receptivity as well as oocyte maturation. Activated thrombocytes rapidly release the contents of intracellular granules and have multiple adhesion molecules and receptors on their surface. Considering the numerous homeostatic endocrine functions of thrombocytes, it is reasonable to suppose a platelet-associated regulatory system (PARS) in reproduction. Although we are far from a complete understanding of the regulatory processes, the results of PARS research and the therapeutic application of aspirin and PRP during in vitro fertilization are promising. Full article

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis. Full article

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD (p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days (p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients (p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women’s reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved. Full article

Problem: Does the presence of hydrothorax suggest that severe ovarian hyperstimulation syndrome (OHSS) is associated with more severe conditions and worse pregnancy outcomes? Method of study: The clinical data for 868 hospital patients with severe OHSS following IVF-ET at Peking University Third Hospital between 1 January 2016 and 21 July 2021 were retrospectively analysed. The patients were divided into two groups, the ascites alone group (n = 417) and the ascites combined with hydrothorax group (n = 451), to investigate the clinical features and pregnancy outcomes of patients with severe ovarian hyperstimulation syndrome (OHSS) combined with hydrothorax plus ascites. Results: The clinical data for 868 hospital patients with severe OHSS following IVF-ET were included. A total of 51.96% of patients with severe OHSS had hydrothorax plus ascites, mainly bilateral and moderate hydrothorax. Most cases with hydrothorax could be monitored and observed, and only 2.66% of the cases required thoracentesis and pleural drainage. Clinically, the time to visit due to worsening symptoms was longer; the hospital stay was shorter; and the OHSS-related laboratory tests, such as white blood cells (WBC), haematocrit (HCT), and ovarian diameter, were less severe in the ascites combined with hydrothorax group than in the ascites alone group. For live-birth outcomes of IVF-ET, the presence and the volume of hydrothorax were not independent risk factors, while the late onset of OHSS (odds ratio [OR]: 0.857 95% confidence interval [CI]: 0.795, 0.925) and a history of foetal reduction (OR: 13.796 95% CI: 1.808, 105.288) were independent protective factors for live birth. Conclusions: Patients with severe OHSS combined with hydrothorax plus ascites have less severe clinical manifestations and laboratory tests than those with ascites alone. The presence and the volume of hydrothorax are unrelated to live-birth outcomes following in vitro fertilization and embryo transfer (IVF-ET). Full article

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for the prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analyses of randomized controlled trials (RCTs) and assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identified, analyzed in terms of safety/efficacy ratio and risk of bias, and graded using the Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In the IVF population not at a high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of a GnRH antagonist may reduce OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have been shown to be promising. Full article

Background: In vitro maturation (IVM) is indicated in women with polycystic ovary syndrome (PCOS) who have a very good ovarian response during in vitro fertilization (IVF) and are therefore at high risk of ovarian hyperstimulation syndrome (OHSS). According to the latest practice committee document, IVM could be a major advance in assisted reproductive technology (ART) procedures (reduced cost and simplified treatment); nevertheless, retrospective studies of IVM versus IVF still demonstrate lower chances of a live birth with IVM. Could IVM prove to be an optimal first-line treatment approach? And limited information is available concerning the success of the subsequent IVF cycle after the failure of an IVM cycle. Does IVM treatment adversely affect the subsequent IVF cycle, and is this worth considering before performing the IVF cycle for women with PCOS? Methods: This prospective nested case–control study at the Peking University Reproductive Medicine center in China was performed between March 2018 and September 2020. Women aged 20–38 years with PCOS and infertility and who were scheduled for their first IVF attempt were eligible. A total of 351 women were randomly allocated to receive one cycle of unstimulated natural IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol followed by hCG as an ovulation trigger (n = 176). This study involved 234 women (58 women with no blastocysts in the first IVM cycle and 158 women who underwent the first IVF cycle). Cumulative live birth rate at 12 months after oocyte retrieval and OHSS of a standard controlled ovarian stimulation (COS) IVF cycle were compared between 58 women in an IVF cycle following a failed IVM cycle and 158 women who underwent the first IVF cycle. Results: No significant differences were found in the cumulative live birth rate (CLBR), ongoing pregnancy rate, or clinical pregnancy rate at 12 months after oocyte retrieval between the two groups (56.9% vs. 58.9%, p = 0.795; 58.6% vs. 60.8%, p = 0.776; and 84.5% vs. 76.0%, p = 0.178). The incidence of moderate-to-severe OHSS was not significantly different between the groups (6.9% vs. 5.7%, p = 0.742). Additionally, there were no significant differences in the total gonadotropin dose, stimulation duration, number of retrieved oocytes, number of retrieved mature oocytes, or fertilization rates. Conclusions: Even if the first IVM attempt failed in subfertile women with PCOS, comparable cumulative live birth rates were observed in the subsequent IVF cycle. IVM treatment does not adversely affect the subsequent IVF cycle. Full article

Background: According to the latest practice committee document, in vitro maturation (IVM) is a simple and safe procedure, especially in patients with polycystic ovary syndrome (PCOS). Does switching from in vitro fertilization (IVF) to IVM (IVF/M) help as a rescue infertility treatment for PCOS patients with an unexpected poor ovarian response (UPOR) tendency? Methods: This retrospective cohort study included 531 women with PCOS who had undergone 588 natural IVM cycles or had switched to IVF/M cycles from 2008 to 2017. Natural IVM was performed in 377 cycles, and switching IVF/M was performed in 211 cycles. The primary outcome measure was the cumulative live birth rates (cLBRs), and the secondary outcomes included laboratory and clinical outcomes, maternal safety, and obstetric and perinatal complications. Results: No significant difference was found in the cLBRs between the natural IVM and switching IVF/M groups (23.6% vs. 17.4%, p = 0.05). Meanwhile, the natural IVM group had a higher cumulative clinical pregnancy rate (36.0% vs. 26.0%, p = 0.01), and a decrease in the number of oocytes was obtained in the switching IVF/M group (13.5 vs. 12.0, p < 0.01). The number of good quality embryos in the natural IVM group was 2.2 ± 2.5, and 2.1 ± 2.3 (p = 0.64) in the switching IVF/M group. No statistically significant differences were observed in the number of 2 pronuclear (2PN) and available embryos. Ovarian hyperstimulation syndrome (OHSS) did not occur in the switching IVF/M and natural IVM groups, indicating a highly favorable outcome. Conclusion: In PCOS infertile women with UPOR, timely switching IVF/M is a viable option that markedly reduces the canceled cycle, results in reasonable oocyte retrieval, and leads to live births. Full article