The Significance of Planned Fertility Preservation for Women With Endometrioma Before an Expected Ovarian Cystectomy

Endometrioma is known to reduce the ovarian reserve and the extent of the decrease is more severe when ovarian surgery is performed. Therefore, to prevent this decline in fertility, patients with endometrioma are considered candidates for preoperative fertility preservation (FP). In this study, we evaluate the efficacy of FP in women with endometrioma before planned ovarian surgery. A total of 95 cycles in 62 patients with endometrioma, undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol before an expected ovarian surgery, were enrolled retrospectively. COS outcomes were compared according to endometrioma laterality. Additionally, first COS cycle outcomes in patients with endometrioma were compared with those in infertile patients, or in patients with a benign ovarian cyst using propensity score matching. When multiple COS cycles were performed, the results of cumulative cycles were analyzed. Embryo quality was worse in the bilateral endometrioma group. Compared with the infertile patient group, the patients with endometrioma had significantly lower Anti-Müllerian Hormone (AMH) and fewer numbers of oocytes retrieved (median, 3.3 vs. 1.2, p<0.001; 7.0 vs. 4.0, p=0.009, respectively). Compared with mature oocytes in infertile patients or patients with a benign cyst, mature oocytes were fewer in patients with endometrioma, but this was not statistically significant (median, 4.0 vs. 3.0, p=0.085; 5.5 vs. 3.0, p=0.052, respectively). The median value of the cumulative number of cryopreserved oocytes or embryos was 14.5 up to the fourth cycle compared to 3 up to the first cycle, with cumulative effect. Women with endometrioma should be counseled for FP before planned ovarian cystectomy. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.

The Early Coasting Method during Ovarian Stimulation in Antagonist Protocols with Combined Use of Cabergoline is Useful in Patients with Polycystic Ovary Syndrome

Purpose: This study aimed to investigate the efficacy of withholding gonadotropins (coasting) and early administration of cabergoline in a flexible Gonadotropin-Releasing Hormone (GnRH) antagonist protocol for patients with Polycystic Ovarian Syndrome (PCOS).

Two modified natural in vitro fertilisation (IVF) protocols compared to conventional IVF treatment: Retrospective data from one Danish Fertility Centre

Aim of study: Over the last decade, laboratory procedures in in vitro fertilisation (IVF) have improved. Hyperstimulated ovaries cause an overload of surplus embryos. The present study was designed to evaluate the efficiency of two different modified IVF cycle protocols trying to reduce the load of medication used for IVF: simple IVF (S-IVF), Tamoxifen 40 mg daily from day 2 in the cycle to ovulation induction) and mild IVF (M-IVF), Tamoxifen 40 mg daily and every secondary 150 IU Gonal F until ovulation induction. The study aims to evaluate their efficiency compared with our conventional IVF (C-IVF) using a short antagonist protocol. Methods: A retrospective cohort study including all patients admitted to IVF for unexplained infertility, tubal factor, and male factor. In all stimulated cycles patients aimed at having fresh embryos transferred and surplus good embryos cryopreserved. All patients were recruited in the same period and allocated to the different treatments on their own request. The study was conducted between June 2019 and February 2021. Results: In total the study included 976 IVF cycles. 651 cycles from C-IVF, 145 cycles from S-IVF and 180 cycles from M-IVF. Mean age in the groups were comparable. Mean number of eggs retrieved was 6.1 (C-IVF), 1.2 (S-IVF) and 3.0 (M-IVF). Pregnancy rate per fresh transfer was found to be 29% for C-IVF, 26% in the S-IVF group and for the M-IVF 20%. Conclusion: Modified IVF stimulation protocols may be an important step towards a simpler assisted reproductive technology (ART) approach. More tolerable for women, easier and cheaper for patients and society they maintain acceptable clinical pregnancy rates. Large prospective studies need to be performed in the future.

Fixed Gonadotropin-Releasing Hormone Antagonist Protocol Versus Flexible Progestin-Primed Ovarian Stimulation Protocol in Patients With Asynchronous Follicular Development During Controlled Ovulation Stimulation: A Retrospective Study

Protocols utilizing gonadotropin-releasing hormone (GnRH) antagonists have emerged as mainstream procedures for ovarian stimulation; however, GnRH increases the risk for periodic cancellation of embryos. Therefore, this study aimed to compare the pregnancy outcomes of a fixed GnRH antagonist protocol and a flexible progestin-primed ovarian stimulation (fPPOS) protocol in patients with asynchronous follicular development during controlled ovulation stimulation and to explore the feasibility of converting patients undergoing a fixed GnRH antagonist protocol to an fPPOS protocol. This was the first retrospective study exploring the fPPOS protocol in patients with asynchronous follicular development, and it was conducted in a public reproductive medicine center from January to December 2020. We included infertile women. All participants were scheduled to undergo administration of a GnRH antagonist on the fifth day of controlled ovulation stimulation. The study group included 129 women who were converted from the fixed GnRH antagonist protocol to the fPPOS protocol for their asynchronous follicular development, while the antagonist group consisted of 258 women (ratio 1:2) who proceeded with a fixed GnRH antagonist protocol. On the second or third day of the menstrual period, 100–300 IU/day gonadotropin injections were administered. For patients who were converted to the fPPOS protocol, medroxyprogesterone acetate tablets at 10 mg/day were started on the fifth day of stimulation or when only one leading follicle reached 14 mm and the other follicles were ≤10 mm in diameter, whichever came first. The rates of embryo implantation, clinical pregnancy, and early pregnancy loss were obtained. The number of oocytes retrieved and the number of high-quality embryos in the antagonist group were significantly higher than those in the fPPOS group (P = 0.039 and P = 0.025, respectively). No significant differences in the rates of embryo implantation, clinical pregnancy, and early pregnancy loss were observed between the two groups. Our study found that in patients who were scheduled for administration of GnRH antagonists but presented with asynchronous follicular development on the fifth stimulation day, it was feasible to switch to the fPPOS protocol.

GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve

ObjectiveTo evaluate the efficiency and validity of cessation of cetrorelix on trigger day during gonadotropin releasing hormone antagonist (GnRH-ant)-controlled ovarian stimulation of in vitro fertilization (IVF) cycles.MethodsIn this retrospective study, a total of 1271 patients undergoing initial IVF cycles following the GnRH-ant protocol were enrolled; 832 patients received cetrorelix on trigger day (Group A) and 439 patients ceased cetrorelix on trigger day (Group B). We compared demographic characteristics, embryological and clinical outcomes between the two groups. A Poisson regression model was used to identify factors that significantly affected embryological outcomes. Patients were further divided into subgroups according to anti-Mullerian hormone (AMH) and age, to assess associations between ceasing cetrorelix on trigger day and embryological outcomes.ResultsThere was a significant improvement on embryological outcomes in patients who ceased cetrorelix on trigger day, and there were no significant differences in clinical outcomes or preovulation rates between the two groups. Furthermore, for patients with 1.1 ≤ AMH ≤ 4.7 ng/ml, all embryological outcomes were significantly higher in Group B compared with Group A. For patients with AMH > 4.7 ng/ml, the number of oocytes retrieved, fertilization rate (2PN) of IVF cycles and proportion of day 3 good quality embryos were all significantly higher in Group B. For patients with age < 35 years, all the embryological outcomes, besides the number of available embryos, were significantly higher in Group B than in Group A. There were no differences in embryological outcomes between the two groups when patients were stratified based on age > 35 years or AMH < 1.1 ng/ml.ConclusionGnRH-ant protocol with cessation of cetrorelix on trigger day improved embryological outcomes for young patients or patients with sufficient ovarian reserve, and was effective at preventing preovulation.

Evaluation of GnRH antagonist pretreatment before ovarian stimulation in a GnRH antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial

Background Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol. Methods This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate. Results Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups. Conclusion This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019730. Registered 26 November 2018.

Clomiphene Citrate Priming Increases Sensitivity During Ovarian Stimulation in Poor Ovarian Responders Undergoing In Vitro Fertilization Treatment: A Retrospective Cohort Study

Background: Since ovarian stimulation was introduced as an assisted reproductive technology, poor ovarian response (POR) management has challenged clinicians. Guidance on optimally managing patients with poor response and/or low sensitivity to ovarian stimulation is still lacking. We aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. Methods: This single-center retrospective cohort study included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. Results: Total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter in the study group. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300-1.933, P = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were directly associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients stimulated by the CC priming antagonist protocol were administered less gonadotropin (1,739.09 ± 719.39 vs. 3,114.77 ± 1,171.23, P < 0.001) at a lower gonadotropin dosage per follicle (637.36 ± 373.05 vs. 1286.26 ± 976.66, P < 0.001) and for a shorter duration (6.58 ± 2.23 vs. 9.80 ± 1.90, P < 0.001). Conclusions: The CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.