Search Results (65)

Objectives: This retrospective single-center cohort study aims to evaluate the impact of dual-trigger therapy (recombinant hCG [rhCG] combined with GnRH agonist) compared to rhCG alone on ART outcomes in women undergoing GnRH antagonist protocols. Methods: Data from 1291 IVF cycles performed between 2016 and 2022 were analyzed. After propensity score matching (PSM) to adjust for confounders, 395 cycles in each group were compared. Primary outcomes included the total number of oocytes retrieved, while secondary outcomes assessed mature oocytes, fertilization rates, and embryo numbers. Results: Dual-trigger therapy yielded significantly more total oocytes (7.50 ± 5.23 vs. 6.12 ± 4.23, p < 0.001) and mature oocytes (5.67 ± 3.87 vs. 5.01 ± 3.13, p = 0.047) compared to rhCG alone. Cycles with no oocytes were fewer in the dual-trigger group (1.3% vs. 3.8%, p = 0.015). Total embryos were also higher with dual trigger therapy (2.43 ± 1.90 vs. 2.00 ± 1.93, p = 0.001). In intracytoplasmic sperm injection (ICSI) cycles, the fertilization rate significantly improved with dual trigger (64.93 ± 33.50% vs. 52.22 ± 34.12%, p = 0.003). No significant differences were noted in fertilization rates for standard IVF (55.14 ± 30.72% vs. 52.29 ± 32.11%, p = 0.18) or maturation rates (72.52 ± 26.91% vs. 71.53 ± 24.75%, p = 0.37). Conclusions: These findings demonstrate that dual-trigger therapy improves ART outcomes by increasing oocyte and embryo yields. Full article

Objectives: Gonadotropin-releasing hormone (GnRH) antagonist protocols are preferred in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) as they provide the best combination of flexibility, acceptable outcomes, and safety. Numerous studies have compared outcomes between GnRH agonist long protocol and standard flexible antagonist protocol. However, there are scant studies investigating the effectiveness of antagonist administration from day 1 of ovarian stimulation in PCOS patients. Methods: We performed a retrospective cohort study to compare laboratory and clinical outcomes in IVF between standard flexible day 5/day 6 versus day 1 GnRH antagonist protocol in PCOS patients. Results: Our data indicates significantly superior oocyte yield and top-quality embryo proportion in patients with antagonists from day 1. Cumulative clinical pregnancy rates also tended to be superior in this group. Conclusions: Our findings indicate that administration of GnRH antagonists from day 1 of stimulation in PCOS patients undergoing IVF may lead to superior results. Full article

Background/Objectives: Mitotane is a key component in the treatment of adrenocortical carcinoma (ACC), but its endocrine side effects in children remain under-characterized. Methods: We conducted a retrospective analysis of 11 pediatric patients (6 males, 5 females) diagnosed with ACC and followed between 2000 and 2025. Seven received mitotane therapy. Data included age at diagnosis, treatment duration and dosage, serum mitotane levels, and endocrine complications. Results: The mean age at diagnosis was 6.6 ± 1.45 years, with a mean follow-up of 10.05 ± 2.45 years. Patients received mitotane for an average of 2.5 ± 0.54 years, with a mean daily dose of 2805.5 ± 145.82 mg and a mean serum level of 16.1 ± 5.92 mg/mL. All mitotane-treated patients developed adrenal insufficiency, requiring supraphysiological hydrocortisone replacement. Four also required mineralocorticoid therapy. Five developed precocious puberty; two males presented with prepubertal gynecomastia; three females were managed with GnRH analogs or aromatase inhibitors followed by estrogen receptor antagonists. Four patients developed central hypothyroidism, treated with levothyroxine. A positive correlation was found between mean serum mitotane levels and the onset of precocious puberty (p = 0.04), while mitotane levels correlated negatively with the development of central hypothyroidism (p = 0.001). Conclusions: Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment. 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

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health. 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

Objective: Most studies concentrate on comparisons between the cleavage stage and blastocyst stage of embryos during in vitro stimulation treatment. We aimed, in this study, to compare the pregnancy rates of day 4 or day 5 blastocyst transfers, all derived from fresh, antagonist-regulated in vitro fertilization (IVF) cycles, and to evaluate the factors affecting pregnancy success. Methods: This retrospective cohort study evaluated 3681 fresh embryo transfer cycles conducted at a private IVF center between 2019 and 2021. Patients were divided into two groups based on the day of embryo transfer: day 4 (Group 1) and day 5 (Group 2). Subgroup analyses were performed according to age (≤40 vs. >40 years) and the number of oocytes retrieved (≤4 vs. >4). All patients underwent ovarian stimulation with FSH alone or in combination with hMG, and GnRH antagonist protocols were used for pituitary suppression. Final oocyte maturation was triggered with recombinant hCG, and fertilization was achieved via intracytoplasmic sperm injection (ICSI) for all cases. Embryos were cultured in sequential media and assessed daily until transfer on day 4 or day 5, based on embryo morphology and clinic logistics. Results: Pregnancy was more likely among women under 40 than among women over 40. There were a total of 1217 women who underwent day 4 transfer and 2464 women who underwent day 5 transfer. A total of 660 (54.2%) of the women transferred on day 4 developed pregnancy. Among those transferred on day 5, 1610 (65.3%) developed pregnancy. When compared to the 4th day, a single embryo transfer on the 5th day enhances pregnancy success by 1.8 times, while two embryo transfers raise it by 1.6 times. Furthermore, when the number of oocytes is greater than four and the number of embryos transferred is two, the pregnancy success rate is 2.5 times higher when embryo transfer is performed on the fifth day versus the fourth day. Regardless of age, oocyte count, or number of embryos transferred, 5th-day fresh embryo transfers enhanced pregnancy success by 1.9 times compared to 4th-day transfer. Conclusions: Transfers of fresh embryos on day 5 are superior to those on day 4 and should be favored, especially for people over the age of 40, regardless of the number of embryos transferred, even if that individual has fewer than four oocytes. Full article

Background: Endometriosis is one of the most common gynecological diseases, affecting up to 10–15% of women of reproductive age. It is a chronic, estrogen-dependent condition that often presents with heterogeneous symptoms, complicating diagnosis and delaying treatment. Methods: This is a narrative review based on a comprehensive analysis of recent literature regarding hormonal treatment options for endometriosis, including primary and adjuvant therapies. Results: Combined oral contraceptives (COCs) are effective in reducing dysmenorrhea, but show limited benefit for other symptoms and may not prevent disease progression. Progestins, particularly dienogest, demonstrate superior long-term efficacy with favorable side-effect profiles. GnRH agonists and antagonists are reserved for second-line treatment due to side effects and hypoestrogenism, but can significantly reduce endometriotic lesions. The levonorgestrel intrauterine system (LNG-IUS) is especially effective in patients with adenomyosis. Conclusions: Hormonal therapies are central to the management of endometriosis. Progestins are considered the most suitable long-term option. Despite promising results, evidence quality varies, and further studies are needed to establish long-term efficacy, patient-specific outcomes, and direct comparisons between agents. Full article

Background and Objectives: The aim of this study is to evaluate the relationship between serum estradiol (E2) levels measured on the day of antagonist administration and live birth rates (LBRs) in women undergoing IVF-ET with an antagonist protocol. Materials and Methods: Data from women who underwent IVF-ET with an antagonist protocol between 2011 and 2023 were retrospectively analyzed. Patients were divided into five groups on the basis of serum E2 levels measured on the day of antagonist administration (Group I: E2 < 400 pg/mL, Group II: 400 ≤ E2 < 650 pg/mL, Group III: 650 ≤ E2 < 800 pg/mL, Group IV:800 ≤ E2 < 1000 pg/mL, and Group V: E2 ≥ 1000 pg/mL). The independent effect of serum E2 levels on live birth was analyzed via an adjusted regression model. Results: A total of 1613 patients were included in the study. The overall LBR was 32.1%. The LBRs for Groups I, II, III, IV, and V were 28.9%, 37.8%, 26.4%, 32.2%, and 34.1%, respectively (p = 0.017). In the adjusted regression model, serum E2 levels measured on the day of antagonist administration < 400 pg/mL (OR: 0.752, 95% CI: 0.580–0.999, p = 0.048) and 650 ≤ E2 < 800 pg/mL (OR: 0.595, 95% CI: 0.388–0.911, p = 0.011) were identified as factors that reduce the likelihood of a live birth, adjusting for age, infertility duration, body mass index (BMI), cycle number, quality of embryo, and number of embryos transferred. Conclusions: The serum E2 level associated with the highest LBR in women undergoing IVF-ET with an antagonist protocol was found to be in the range of 400–650. Serum E2 levels < 400 pg/mL or in the range of 650–800 pg/mL were statistically significantly associated with a reduced LBR. Full article

Background/Objectives: Poor responder patients represent the greatest challenge in ART. An inadequate response to COS strongly correlates with a reduced chance of conception. A novel classification of poor responders overcame a deficiency in the Bologna criteria and distinguished an expected and unexpected low ovarian response, allowing for an individual treatment approach to be created. In this study, we compared the clinical outcomes in poor responders, according to two different ovarian stimulation protocols, GnRH agonists and antagonists, classified according to the Poseidon criteria, to determine the most effective protocol for each group. Methods: This retrospective study involved 1323 low-prognosis women ranked according to the Poseidon classification and a control group of normal responders. Results: The GnRH-antagonist protocol showed some advantage in the Poseidon 1b group whereas the GnRH-agonist protocol was more effective in the Poseidon 4 group. There were no differences in live births or miscarriage rates in poor responders among these two protocols. Conclusions: Using both the agonist/antagonist approaches, live birth rates are two or even three times less in Poseidon patients in comparison to normal responders. The number of obtained oocytes, their maturity and quality, and women’s ages were found to be the most influential determinants for a successful outcome. Further investigations into ovarian stimulation strategies are required to enhance oocyte number and live birth occurrence. Full article

Background/Objectives: Unexpected low responders are patients with normal ovarian reserve tests who exhibit suboptimal responses to stimulation but have promising treatment potential due to adequate follicle availability. This study aimed to compare the live birth rates (LBRs) between fixed and flexible gonadotropin-releasing hormone antagonist (GnRH-ant) protocols in low-prognosis patients from Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) groups 1 and 2. Methods: This retrospective cohort study included 117 women classified as POSEIDON groups 1 and 2 who underwent GnRH-ant protocols for in vitro fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) at the Petrova Maternity Hospital in Zagreb (2019–2020). The primary outcome analyzed was the live birth rate (LBR). The secondary outcomes were the GnRH start day, duration of gonadotropin therapy, number of oocytes, number of embryos, number of blastocysts, number of third-day embryos, number of vitrified embryos, positive pregnancy test, clinical pregnancy, and miscarriage rate. Group comparisons were conducted using Mann–Whitney and chi-squared tests. Results: In POSEIDON group 1, the fixed protocol significantly improved outcomes, with higher rates of clinical pregnancy, 12-week ongoing pregnancy, and LBRs (58.8% vs. 8.3%). More fresh transferable embryos were also noted (p < 0.05). In POSEIDON group 2, no significant differences were observed between protocols for any outcomes. Conclusions: The fixed GnRH-ant protocol improved pregnancy outcomes for POSEIDON group 1 but showed no advantage over the flexible protocol in POSEIDON group 2. Full article

Objectives: The downregulation of anti-adhesive regulatory proteins and upregulation of adhesive genes are critical for the receptive endometrium. This study was designed to determine whether switching between the anti-adhesive podocalyxin (PDX) and adhesive HOXA10 receptivity modulator occurs in the endometrium of women with recurrent implantation failure (RIF). Methods: Twenty-four patients with RIF who could not conceive for three or more cycles despite good-quality embryo transfer constituted the study group. Twenty-four patients with unexplained infertility (UEI) matched for age, BMI, and infertility duration were included in the control group. Twenty women scheduled to undergo intrauterine device (IUD) placement for birth control were included in the comparative group. Endometrial tissue was collected from patients with RIF and UEI during egg retrieval after ovarian stimulation using the GnRH antagonist protocol. In the fertile group, endometrial tissues were collected during IUD insertion. HOXA10 mRNA expression was analyzed by qRT-PCR and PDX protein expression was analyzed by ELISA. The relative expression of endometrial HOXA10 mRNA was calculated using the 2^−ΔΔCt equation. Results: The relative expression of HOXA10 mRNA in the RIF group was significantly lower than that in the UEI group (p < 0.001). HOXA10 mRNA expression in the fertile group was significantly higher than that in the RIF group and was similar to that in the UEI group. PDX expression in the RIF group was significantly higher than that in the UEI group (p < 0.001). PDX expression in the fertile group was significantly lower than in the RIF and UEI groups. A negative correlation was detected between the anti-adhesive PDX protein and adhesive HOXA10 (r = −0.797, p < 0.001). Although there was a positive correlation between endometrial thickness recorded on the day of hCG administration and HOXA10 (r = 0.590, p < 0.01), endometrial thickness was negatively correlated with PDX (r = −0.529, p < 0.01). Conclusions: The failed physiological downregulation of the anti-adhesive PDX protein in patients with RIF prevented the upregulation of adhesive HOXA10 mRNA. Full article

Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists’ clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases. 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

Objective: To assess the effect of hysteroscopic polypectomy on the in vitro fertilization (IVF) results in infertile women with at least one prior negative IVF outcome. Methods: This retrospective cohort study included women who had attended the “2nd Department of Obstetrics and Gynecology of the National and Kapodistrian University of Athens” and “Iaso” Maternity Hospital from October 2019 to January 2023 for infertility treatment. The medical records of 345 women aged 18–45 years old without abnormal findings in hysterosalpingography (HSG) and with at least one previous failed IVF procedure were analyzed. The male factor was excluded, as well as a prior hysteroscopic removal of polyps. In 67 women, polyps were suspected during initial two-dimensional ultrasound (2D-US) examination. The final sample of the study comprised 40 patients, in which endometrial polyps were removed by hysteroscopy with the use of resectoscope. All patients underwent ovarian stimulation and IVF in the consecutive cycle using a short GnRh antagonist protocol. Main Results: After hysteroscopic polypectomy, 29 (72.5%) out of 40 patients had a positive pregnancy result: 26 (65%) clinical and 3 (7.5%) biochemical pregnancies were documented. There was a statistically significant difference between the number of clinical pregnancies before and after polypectomy (p < 0.001), as well as between the total number of pregnancies (p < 0.001). Secondary Results: Women with positive outcome were significantly younger and had significantly lower FSH levels (p < 0.007). They also had significantly higher AMH (p < 0.009) and peak estradiol levels (p < 0.013) and yielded more M II oocytes (p < 0.009) and embryos (p < 0.002). Conclusions: Hysteroscopic polypectomy in women with a suspected endometrial polyp using 2D ultrasound and a history of prior failed IVF attempt improves IVF outcomes in terms of the clinical and total number of pregnancies. Full article