Ovarian Stimulation Protocols Research Articles

A multicycle approach through DuoStim with a progestin-primed ovarian stimulation (PPOS) protocol: a valuable option in poor prognosis patients undergoing PGT-A.

This study is to evaluate the effectiveness of a PPOS protocol in poor prognosis patients undergoing IVF with DuoStim and PGT-A versus the conventional protocol with GnRH antagonist. Retrospective cohort study encompassing 444 couples obtained matching one PPOS-DuoStim with two antagonist-DuoStim cycles at a private IVF center between 2020 and 2023 (averagematernal age: 40years, averagecumulus-oocyte complexes collected after the first stimulation: 5). The study was powered to exclude a two-sided different euploid blastocyst rate per MII oocytes (EBR per MII) in the two groups (alpha = 0.05, power = 0.9, effect size = 0.3). All cycles involved ICSI, blastocyst stage PGT-A, and single vitrified-warmed euploid transfers. We compared all embryological and clinical outcomes within each group (first vs. second stimulations), and among the two study arms (first stimulation vs. first stimulation; second stimulations vs. second stimulation; overall). The overall EBR per MII was the primary study outcome. The cumulative-live-birth-rate per concluded cycles (CLBR) was the main secondary outcome. In the second stimulations, we obtained a greater number of COCs and MIIs in both antagonist- and PPOS-DuoStim groups. No difference was observed for all embryological and clinical outcomes when comparing the two stimulations within each group. All embryological and clinical outcomes were comparable also between the two groups, including the EBR per MII. To date, 285 and 121 antagonist- and PPOS-DuoStim cycles were concluded. The CLBR was comparable between the groups: 26% vs. 29%. PPOS-DuoStim holds potential for being an efficient, patient-friendly, and possibly cost-effective approach that does not compromise treatment efficacy. Future investigations must explore PPOS effect on follicular recruitment, neonatal, and long-term outcomes.

Oocyte maturity rate is an age-independent predictor of blastocyst development and euploidy rates: a multicenter retrospective study

Research Question Can oocyte maturity rate predict blastocyst development and euploidy rates independently of patient age? Design A multicenter retrospective study including 1547 consecutive women undergoing first in-vitro fertilization cycle of oocyte retrieval-intracytoplasmic sperm injection with preimplantation genetic testing for aneuploidy (IVF/ICSI/PGT-A). Both centers used the same PGT lab for PGT-A testing. Oocyte maturity rate as a predictor for cycle outcomes of blastocyst development and euploidy rates was analyzed by Poisson regression model, after controlling for other known confounders. Results Oocyte maturity rate is positively correlated with blastocyst development rate and euploidy rate after controlling for patient age at cycle start, BMI, AMH levels, total FSH dosage, number of days of ovarian stimulation, and peak estradiol level (p<0.01). Conclusion This study demonstrated that oocyte maturity rate can predict blastocyst development and euploidy rates independently of other confounding factors including patient age. This finding suggests that oocyte maturity rate may serve as an important biomarker for oocyte quality. This can be used by physicians to evaluate and improve the efficacy of ovarian stimulation regimens for IVF. This may further enhance artificial intelligence (AI) capabilities in optimizing ovarian stimulation protocols and outcomes of Assisted Reproductive Technologies (ART).

Impact of Omicron Variant Infection on Female Fertility and Laboratory Outcomes: A Self-Controlled Study.

Investigating the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on female fertility and laboratory outcomes in patients undergoing assisted reproductive technology (ART) treatment who were initially uninfected but later became infected. This self-controlled study included 197 patients who underwent repeated oocyte retrieval before and after SARS-CoV-2 infection between March 2021 and April 2023, of which 117 used the same ovarian stimulation protocol within a consistent age range. We evaluated the ovarian reserve, ovarian response, and laboratory outcomes in patients before and after SARS-CoV-2 infection. The ovarian reserve (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estrogen [E2], anti-Müllerian hormone [AMH], antral follicle count [AFC]), ovarian response (total Gn dosage, duration of Gn administration, number of follicles ≥14mm on trigger day, number of retrieved oocytes), and laboratory outcomes (cleavage stage good-quality embryo rate, blastocyst formation rate, and cycle freezing rate) showed no significant differences before and after SARS-CoV-2 infection in 117 patients (p>0.05). When stratified by age, the ≤ 35years group showed a higher two pronuclei (2PN) fertilization rate post-infection, while the >35years group had increased mature metaphase II (MII) oocyte and blastocyst stage good-quality embryo rates. Additionally, upon stratified by the time interval between SARS-CoV-2 infection and ART treatment, in the ≤ 3months group, there was an increased post-infection MII oocyte rate, 2PN fertilization rate, and blastocyst stage good-quality embryo rate. Meanwhile, no significant differences were found in any indicators when the interval exceeded threemonths. Our study suggested that undergoing IVF/ICSI treatment after recovering from COVID-19 may not adversely affect female fertility and laboratory 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.

Melatonin levels in the follicular fluids and its correlation with ICSI Outcomes

Background: Melatonin is a hormone mainly synthesized and secreted from the pineal gland. The daily rhythm of circulatory melatonin is released in very low concentrations during the day and high levels at night. Melatonin has many functions beside regulation of circadian rhythm including immune system and autonomic cardiovascular regulation but the main melatonin function is antioxidant action and detoxification of free radicals. Patients and method: This cross sectional study was conducted during the period starting from November 2018 to May 2019. Eighty infertile female aged range 18–46 years were enrolled in the present study, the patients were undergoing controlled ovarian induction for IVF /ICSI treatment. All patents were divided into 3 groups according to age, FSH, E2, AMH and ovarian respond to controlled ovarian stimulation (COS) protocols. The follicular fluid melatonin measured at oocyte retrieval day using enzyme linked immunosorbent assay (ELISA). Results: There was significant difference in follicular fluid melatonin level between the three studied groups (p=0.031). There was also a positive significant correlation between follicular fluid melatonin with MII oocytes (r=0.343; p= 0.024), grade I embryo (r=0.375; p= 0.003) and AMH (r = 0.279; p= 0.027), on the other hand there was a negative significant correlation between follicular fluid melatonin and serum FSH (r = - 0.331; p= 0.016). There was also no significant difference of follicular fluid melatonin levels between pregnant and non-pregnant females (p=0.083). Conclusion: Melatonin levels in follicular fluid improve the oocytes and embryo qualities but have no effect in positive pregnancy rate.

REPRODUÇÃO ASSISTIDA: DESAFIOS E AVANÇOS DAFERTILIZAÇÃO IN VITRO E INSEMINAÇÃO ARTIFICIAL COM PERSPECTIVAS ATUAIS E FUTURAS

Assisted human reproduction (AHR) is a set of medical techniques that enable human reproduction with assistance, contributing to cases of infertility, advanced age, same-sex couples, independent gestation, and family planning. The main techniques are artificial insemination and in vitro fertilization (IVF). This exploratory-descriptive study investigates the challenges faced by these couples, as well as recent advancements and future perspectives of these techniques. The analysis includes a review of recent literature, focusing on advancements such as improved ovarian stimulation protocols and embryo selection, as well as the impact of emerging technologies. The study also addresses the variable success rates, procedure costs, and ethical issues involved. It is expected that ongoing innovations will improve success rates, reduce risks, and enhance the accessibility of these treatments. Currently, the technique of intracytoplasmic sperm injection (ICSI) is widely used. Despite the challenges, AHR has enabled infertile couples to realize their dream of parenthood. With scientific and technological advancements, it is anticipated that AHR techniques will continue to evolve to benefit more and more couples wishing to have children.

Progestin-primed ovarian stimulation outcomes in in-vitro fertilization (IVF) – A systematic review of the literature

Background: Progestin-primed ovarian stimulation (PPOS) stimulates ovaries to block the premature surge of luteinizing hormone (LH) by using micronized progesterone or a progestin during the follicular phase instead of the conventional gonadotropin-releasing hormone (GnRH) analogues or GnRH antagonists downregulating LH to obtain multi-follicle engagement. Current work aims to assess the influence of progestogen treatment on ovarian stimulation and the ability to control LH surge, its efficacy and suitability in retrieving oocytes, without affecting the embryo quality and its benefit among infertile women long-term outcomes on children compared to standard stimulation protocols. Materials and Methods: The literature review used the randomized control trials published in the Pubmed database from January 2015 to April 2021. To generate the citation list, the following keywords were used: ‘progestin-primed ovarian stimulation’, ‘PPOS’, ‘micronized progesterone’, ‘medroxyprogesterone’, and/or ‘dydrogesterone’. The selected articles analyzed the cohort, intervention, and scheme of the progestin-primed ovarian stimulation protocol in controlled ovarian stimulation (COS) for in-vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI) used in Assisted Reproductive Technologies (ART). Results: Overall we concluded that PPOS for IVF/ICSI in ART results in a higher number of obtained embryos, lower incidence of OHSS, equal duration of stimulation, number of retrieved oocytes, and number of MII oocytes. It is also suggested that long-term safety in children shows no significant difference between the study and control groups. Conclusions: Despite the outcomes of progestin stimulation cycles among all cohorts, we concluded that poor ovarian responders, patients with PCOS, women of advanced age and oocyte donors benefit the most from using PPOS.

Does hCG-trigger in the mild stimulation protocol for endometrial preparation have any effect on pregnancy outcome in frozen-thawed embryo transfer?

BackgroundRecent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles.MethodsIn the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles.ResultsDemographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41–3.86, P-value = 0.001).ConclusionPregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field.

Impact of letrozole co-treatment in an antagonist protocol for IVF/ICSI: a retrospective study

ObjectiveThe present study aimed to investigate the impact of combined use of letrozole in an antagonist protocol during IVF on live birth outcomes and to assess the safety of letrozole in terms of maternal and neonatal complications.MethodsThis retrospective cohort study included women undergoing IVF/ICSI and fresh embryo transfer (ET) treatment with and without letrozole co-treatment from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). The primary outcome was the live birth rate, while the incidences of maternal and neonatal complications were secondary outcomes. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the analyzed outcomes. Sensitivity analysis was performed using a propensity score-based patient-matching (PSM) model, an inverse probability weighting (IPW) model, logistic regression models with women undergoing their first IVF-ET cycle, and subgroup analysis.ResultsOf the 4780 women enrolled in the study, 3887 underwent an antagonist protocol for ovarian stimulation, while 893 received letrozole co-treatment. In this cohort, letrozole co-treatment demonstrated comparable live birth rates to the use of antagonist protocol alone (logistic regression: aOR, 0.88; 95% CI, 0.71–1.08; PSM: aOR, 0.97; 95% CI, 0.77–1.22; IPW: aOR, 0.88; 95% CI, 0.71–1.10). Notably, individuals with a body mass index (BMI) exceeding 24 and those with high ovarian response experienced higher live birth rates under the letrozole co-treatment regimen (BMI ≥ 24: aOR, 1.85; 95% CI, 1.14-3.00; high response: aOR, 1.60; 95% CI, 1.02–2.50). Letrozole co-treatment was also associated with decreased risks of gestational diabetes (aOR, 0.34; 95% CI, 0.15–0.69) and small for gestational age (SGA) fetuses (aOR, 0.42; 95% CI, 0.22–0.75) in fresh ET cycles. These finding were robust in both PSM and IPW models.ConclusionsOur findings suggested that letrozole co-treatment in antagonist protocol for IVF/ICSI was associated with a comparable live birth rate following fresh ET. Further prospective randomized studies are needed to verify our results.

Effects of ovarian stimulation on embryo euploidy: an analysis of 12874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.

Does ovarian stimulation and the ovarian response affect embryo euploidy? Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy. Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue. A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021. A total of 617 women with 867 PGT-M cycles involving 12874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos). Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all P > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (P = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (P = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (P = 0.001, <0.001, and 0.012, respectively). Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors. Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased. This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest. N/A.

Comparison of highly purified human menopausal gonadotropin and recombinant follicle stimulating hormone use in patients undergoing in vitro fertilization with progestin-primed ovarian stimulation protocol: a single center retrospective analysis.

Recently, progesterone has been used to prevent LH surge instead of GnRH analogues during ART treatments, which is known as progesterone-primed ovarian stimulation (PPOS) protocol. During ART treatment, highly purified human menopausal gonadotropin (HP-hMG) and recombinant follicle stimulating hormone (rFSH) are two of the agents used for stimulation of antral follicles. The aim of this study is to compare the efficacy and success of HP-hMG and rFSH agents in the ovarian stimulation step of the PPOS protocol, which has not been previously reported in the literature. This retrospective study was conducted at a university hospital with patients who underwent IVF treatment using PPOS protocols in between January 2019 and July 2021. For ovarian stimulation, rFSH was used in group I and HP-hMG was used in group II. Mature oocyte ratio was the primary outcome, and live birth rate was the secondary outcome. Mann-Whitney and Chi-square tests were used for statistical analysis. All p values below 0.05 were considered significant. Total numbers of follicles, oocytes, MII, and 2PN numbers obtained were similar between the two groups. The fertilization rates were 66.7% in the rFSH group and 64.3% in the HP-hMG group (p > 0.05). The pregnancy rates were 53.5% and 46.7% in the rFSH and HP-hMG groups, respectively. There was no statistically significant difference between pregnancy, abortus, and live birth rates. In this study, it is demonstrated that stimulation of oocytes with either rFSH or hMG in the PPOS protocol, which has been added to IVF treatment protocols in recent years, had no statistical difference regarding mature oocyte numbers and live birth rates between the two groups. These results are consistent with the previous literature which compared rFSH and hMG in GnRH agonist and antagonist protocols.

Dual trigger or hCG alone: A retrospective analysis on patients with diminished ovarian reserve under in vitro fertilization and embryo transfer (IVF-ET) treatment

ObjectiveWith remarkable deficiency in both oocyte stock and competence, the prognosis of IVF-ET in diminished ovarian reserve (DOR) is obstinately poor, underscoring warranted optimization to current procedures. We compared the efficacy of dual-trigger (hCG plus GnRH-a) and hCG alone on the outcomes for DOR patients. Study designA total of 381 couples and 857 controlled ovarian stimulation (COS) cycles, and 222 couples and 366 frozen embryo transfer (FET) ones were included. The intermediate outcomes during oocyte retrieval and in vitro culture were compared based on COS dataset, while outcomes after embryo transfer analyzed based on FET dataset. The marginal effect of all study factors and covariates were evaluated with a cluster-weighted GEE model. Results and conclusionNeither the intermediate nor implantation outcomes were improved by dual-trigger. The OR values were 1.08 (95 % CI: 0.41–2.78) for retrieval cancellation, 1.33 (95 % CI: 0.89–2.00) for oocyte harvest, 1.04(95 %CI: 0.94–1.15) for viable embryo and 1.03(95 %CI: 0.88–1.19) for top-quality embryo. Similarly, the ORs were 0.90 (95 %CI: 0.62–1.30) for implantation and 0.97 (95 %CI: 0.56–1.69) for clinical pregnancy. This equivalence remained unchanged after adjusting for the covariates such as age, BMI, controlled ovarian stimulation protocols, etc. Thus, dual-trigger cannot provide significant advantage over hCG in related to immediate or clinical outcomes of IVF-ET treatments in DOR patients.

Significance of FSHR and LHCGR gene polymorphisms on clinical outcomes in gonadotropin-releasing hormone antagonist protocol with freeze-all strategy: A case-control study.

Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear. This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles. Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant follicle-stimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant. Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage. The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

Programming the onset of ovarian stimulation: from early follicular phase start to oral contraceptive pill, to luteal phase E2, Duostim, and random start oral contraceptive protocols

Ovarian stimulation has been the single most efficient measure ever taken in assisted reproductive technology for improving outcomes by harvesting multiple oocytes and ultimately, embryos. Today, ovarian stimulation protocols consist of administrating exogenous gonadotropins to override the natural mechanisms that control the ovulatory quota to one in humans. For practicality issues, there have been numerous attempts to control, or "program," when ovarian stimulation is initiated to improve functionality and in turn efficacy for assisted reproductive technology programs. The different options for controlling the onset of ovarian stimulation currently available are discussed here, as well as the novel possibility of using progestins for blocking premature ovulation.

Cost-Effectiveness of Clomiphene Citrate-Based Minimal Stimulation Compared with Controlled Ovarian Stimulation Protocol in Women with Diminished Ovarian Reserve

Background: In Japan, where infertility treatment is now covered by insurance, appropriate protocols for patients with diminished ovarian reserve (DOR) based on treatment outcomes and cost-effectiveness must be selected. Therefore, this study aims to provide information on the outcomes and cost-effectiveness of conventional ovarian stimulation and mild stimulation for patients with DOR in Japan. Methods: Data from 66 women who underwent first oocyte retrieval at Showa University Hospital between May 2019 and November 2023 were analyzed. Results: The clomiphene citrate (CC) group used significantly fewer gonadotropins and incurred lower costs than the conventional ovarian stimulation group while achieving comparable clinical outcomes, including cumulative live birth rates. Conclusions: CC-based minimal stimulation is a cost-effective alternative to conventional ovarian stimulation for patients with low ovarian reserve without compromising clinical efficacy. Further randomized controlled trials are required to confirm these findings and optimize protocols for this population.

Is there an association between the ‘October 7th’ events and IVF outcomes in Israel?

Research questionIs there an association between the ‘October 7th’ 2023 events and IVF outcomes in Israel? Designin this retrospective cohort study the study group was women treated during the 4 weeks after ‘October 7th’, compared with a matched control group treated between 1 January 2021 and 6 October 2023. Each study group participant was matched with three separate control subjects of the same female age at oocyte retrieval, with a matching body mass index (BMI), IVF cycle number and ovarian reserve parameters. ResultsThe study included 580 patients. The 145 women who underwent oocyte retrieval or frozen embryo transfer after 7 October 2023 were compared with 435 women treated before 7 October. The mean age of the study group was 35.6 ± 6 years, and the mean BMI 24.7 ± 5.3 kg/m2. Pregnancy rates per embryo transfer were similar between the groups (22.4% versus 30.5%, P = 0.28 in fresh cycles; 16.9% versus 27.1%, P = 0.12 in frozen embryo transfers). Among women who underwent oocyte retrieval there were no differences in the ovarian stimulation protocols (P = 0.95), number of oocytes retrieved (P = 0.16) or number of fertilized oocytes (P = 0.34). There was no difference in the rate of good-quality embryos between groups (P = 0.053). Among women who underwent frozen embryo transfers, during the study period more patients had natural cycles (52.5% versus 24%, P < 0.001), and there was no difference in maximal endometrial thickness before embryo transfer (P = 0.33). ConclusionsIt appears that there is no association between the ‘October 7’ events and IVF outcomes.

Granulosa cells provide transcriptomic information on ovarian follicle dynamics in southern white rhinoceros

Much remains unknown about the reproductive physiology of southern white rhinoceros (SWR) and the effect of ovarian stimulation prior to ovum pickup (OPU) have not been fully elucidated. Granulosa cells (GC) provide valuable insight into follicle growth and oocyte maturation status. The goals of this study were to evaluate transcriptomic changes in GC from three stages of follicle development and to identify biomarkers possibly associated with follicular growth and maturation as a result of ovarian stimulation. GC collected from SWRs following OPU were assigned stages based upon follicle size. Total RNA was isolated, and cDNA libraries were prepared and sequenced on a NovaSeq 6000. All bioinformatics analyses were performed utilizing the Galaxy web platform. Reads were aligned to CerSimCot1.0, and the manual curation was performed with EquCab3.0. Overall, 39,455 transcripts (21,612 genes) were identified across follicle stages, and manual curation yielded a 61% increase in gene identification from the original annotation. Granulosa cells from preovulatory follicles expressed the highest number of unique transcripts. The following seven biomarkers were determined based upon cluster analysis and patterns of expression: COL1A1, JMY, FBXW11, NRG1, TMPO, MACIR and COL4A1. These data can be used to potentially evaluate the effects of different ovarian stimulation protocols on follicle dynamics, improve OPU results, and support conservation efforts in this species.

Comparison of fixed and flexible progestin-primed ovarian stimulation in women classified in patient-oriented strategies encompassing individualized oocyte number (POSEIDON) group 4.

This study aimed to compare the fixed and flexible protocols for progestin-primed ovarian stimulation (PPOS) in poor ovarian responders. This retrospective study included 95 poor ovarian responders classified using the Patient-Oriented Strategies Encompassing Individualized Oocyte Number group 4 criteria. Treatment involved assisted reproductive medicine using fixed and flexible PPOS protocols at Shiga University of Medical Science between July 2019 and August 2023. PPOS cycles were assigned to the fixed and flexible groups at the discretion of attending physicians. The results of assisted reproductive medicine were compared between groups. The fixed and flexible groups included 68 and 27 patients, respectively. The flexible group obtained more retrieved oocytes and two pro-nuclei than the fixed group, without an early luteinizing hormone surge. Multiple linear regression analysis demonstrated that differences in protocols and anti-müllerian hormone (AMH) levels were related to the number of retrieved oocytes. The differences in protocols were more strongly correlated with the number of oocytes than with the AMH levels. Among poor ovarian responders, the flexible PPOS protocol provided more retrieved oocytes than the fixed PPOS protocol, possibly because the total dosage of progestins was lower in the flexible group and progestins were not administered at the time when ovarian stimulation was initiated.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

ObjectiveTo compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute.Materials and methodsThis retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART.ResultsOver the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART.ConclusionThe ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis

ObjectivesPregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of...