Co-Administration of Clomiphene Citrate and Letrozole in Mild Ovarian Stimulation Versus Conventional Controlled Ovarian Stimulation Among POSEIDON Group 4 Patients

This retrospective study assessed the effect of the co-administration of clomiphene citrate (CC) and letrozole in mild ovarian stimulation, compared to conventional regimens, among Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 4 patients. There were 114 POSEIDON Group 4 patients undergoing in vitro fertilization treatments with 216 stimulation cycles recruited from a Taiwan’s reproductive center during 2016-2020. Main outcomes were the numbers, quality of retrieved oocytes and embryo development. Pregnancy outcomes were assessed after embryo transfers. Per stimulation cycle, patients receiving mild stimulation with a combination of CC and letrozole (study group) versus those with COS (control group) had lower numbers of pre-ovulatory follicles (2.00 ± 1.23 vs. 2.37 ± 1.23, p=0.0066) and oocytes retrieved (1.83 ± 1.17 vs. 2.37 ± 1.23, p=0.0017), and lower follicular output rate (58.6% vs. 68.38%, p=0.0093) and mature oocyte output rate (44.29% vs. 52.88%, p=0.0386) but a higher top-quality metaphase II oocyte ratio (66.7% vs. 54.59%, p=0.0444) and a similar fertilization rate (91.67% vs. 89.04%, p=0.4660). With adjustment for significant between-group baseline differences using multivariable logistic generalized estimating equation model analyses, there was no statistical difference in oocytes retrieved and embryo development between the study and control groups, and insignificant increases in successful pregnancies in the study group were found compared to the control group (i.e., odds ratios [95% CIs]: 1.13 [0.55, 232] and 1.50 [0.65, 3.49] for ongoing pregnancy and live birth, respectively). For POSEIDON Group 4 patients, cotreatment of CC and letrozole in mild stimulation may increase the high-quality oocyte ratio and yield comparable fertilization rate and pregnancy outcomes.

Frozen Embryo Transfer in Mildly Stimulated Cycle With Letrozole Compared to Natural Cycle in Ovulatory Women: A Large Retrospective Study

ObjectiveTo evaluate the clinical effect of mild stimulation with letrozole on pregnancy outcomes in ovulatory women undergoing frozen embryo transfer (FET) compared to natural cycle.DesignRetrospective observational study.SettingTertiary care academic medical center.PopulationA total of 6,874 infertile women with regular menstrual cycles (21-35 days) met the criteria for this study in the period from 2013 to 2020.MethodsAll patients who were prepared for and underwent FET were divided into two groups: a modified natural cycle (NC) group (n=3,958) and a letrozole cycle group (n=2,916).Main Outcome MeasuresThe primary outcome of the study was clinical pregnancy rate. Secondary outcome measures were endometrial thickness, rates of implantation, positive HCG test, live birth, early miscarriage and ectopic pregnancy.ResultsThe clinical pregnancy rate was not statistically different between the modified NC-FET group and the letrozole-FFT group before (crude OR 0.99, 95% CI 0.90-1.09, P=0.902>0.05) and after propensity score matching (PSM) (crude OR 1.01, 95% CI 0.91-1.12, P=0.870>0.05). After multivariable logistic regression analysis, the clinical pregnancy rate remained insignificant before (adjusted OR 1.00, 95% CI 0.91-1.10, P=0.979>0.05) and after matching (adjusted OR 1.00, 95% CI 0.89-1.11, P=0.936>0.05), respectively. Similarly, in the crude and adjusted analysis, the positive HCG test, implantation, live birth and early miscarriage rates were also comparable in the letrozole-FFT group and modified NC-FET group before and after matching. Furthermore, the endometrial thickness of letrozole-FFT group was similar to that of modified NC-FET group with adjusted analysis.ConclusionOur observation suggests that mild stimulation with letrozole could produce similar pregnancy outcomes in ovulatory patients who undergo FET when compared with a natural cycle.

A cohort study on safety for oocyte retrieval in IVF using the same 20G needle for local analgesia and retrieval. Vaginal cleaning did not add to the safety of the procedure

Aim of study: What is the effectiveness and safety of using a 20G single lumen needle (SLN) for both applying local analgesia (LA) in the vaginal vault and ovarian capsule and oocyte retrieval (OR) using a simple syringe? And will thoroughly cleaning (TC) of the vagina before reducing the risk of the puncture procedure? Using a thin SLN has been postulated to jeopardize cumulus oocyte complexes (COC). Further applying LA in the same needle without retracting the needle before OR has been claimed to harm oocyte development. Also, many clinics extensively clean the vagina before OR. Methods: We performed a retrospective cohort study including 4983 women. 877 underwent no cleaning (nonTC) of the vagina and 4106 underwent TC using NaCl. All had OR with a 20G SLN attached to a syringe for local anaesthesia and egg collection. The treatments were done in one centre during the period from January 2016 to June 2019. We studied women undergoing IVF treatment aged 18–45 years. Women had either thoroughly vaginal cleaning before OR or no cleaning depending on the physicians preferences. All women had LA using Citanest Dental Octapressin 2ml. placed in the vaginal vault in the direction of the intended puncture including in the ovarian capsule. Therefore, only one puncture was needed in both sides, left and right. All punctures were hereafter followed by OR using the same 20G SLN. Aspiration was done by a 20ml syringe handled manually by the physician. All women underwent a conventional antagonist protocol with FSH stimulation and Ovitrelle 250IU for induction or Mild Stimulation using Tamoxifen, FSH and Ovitrelle. Outcome measurement were bleeding measured by the necessity of applying compression after the puncture or infection observed up to 1 month. Results: Baseline characteristics including age, BMI and type of stimulation were comparable between the groups. In the nonTC group no infections, bleedings or abscesses were found. In the TC group there were 1 abscess observed. Intact COC was similar in the two groups as well as pregnancy rates. Conclusion: During OR in ART the use of a 20G SLN using the same needle for LA and hereafter, without changing needle in the puncture channel, continue with the egg collection (EC) is simple and safe. In this situation TC is not necessary before puncture, making the procedure more patients friendly. In women undergoing oocyte retrieval for IVF, we found the use of a 20G SLN for both applying LA and retrieving COC safe, effective and simple. Additional TC of the vagina before puncture did not add more to the safety of the procedure.

P–676 Mild stimulation followed by embryo accumulation via vitrification appears to be beneficial for managing poor ovarian response: A retrospective cohort study including 610 patients

Study question Could embryo accumulation employing mild stimulation cycles prove beneficial for managing patients presenting with poor ovarian response (POR)? Summary answer Embryo accumulation may be an efficient POR management strategy, enabling a higher number and quality cohort of embryos, ultimately improving success results. What is known already It is widely accepted that POR constitutes a challenging condition. The limited oocyte yield associated with POR detrimentally impacts in vitro fertilization (IVF) success rates. Moreover, the documented heterogeneity among POR patients compromises our efforts to successfully address POR, despite the advances noted regarding stimulation protocols employed today. Considering the aforementioned, embryo accumulation following consecutive stimulation cycles has emerged as an alternative management strategy towards increasing the number of available embryos prior to embryo transfer (ET), mimicking normoresponding conditions. However, only few studies have been so far conducted and the need for further data is underlined. Study design, size, duration A single-center retrospective study was conducted in the Centre of Human Reproduction, Genesis-Athens Clinic from January 2015-December 2019. Only patients presenting with POR according to Bologna criteria were included. In total, 610 POR patients were considered eligible and were divided in three groups namely, mild stimulation-fresh ET (150 IUs of gonadotropins) (MILDF), mild stimulation employing embryo accumulation (MILDA), and natural cycle employing embryo accumulation (NATA). Respective comparisons on embryology and pregnancy data are provided. Participants/materials, setting, methods Resulting embryos from the MILDF, MILDA, and NATA groups were cultured up to the cleavage stage and categorized into three groups according to quality, namely top (grade 1), good (grade 2–3) and poor (grade 4–5) (Veeck, 1999). Top and good quality embryos were considered eligible for ET/vitrification. The banking scenario entailed accumulation of at least three embryos, including at least one top quality embryo. Embryo transfers included up to two cleavage stage embryos. Main results and the role of chance Comparing MILDF and MILDA groups, a higher number of available oocytes and embryos was observed in MILDA (2.36±1.15 vs 6.58±1.11; 1.72±1.02 vs 3.51±0.61, P-value<0.001). However, a mean number of 3.90±1.56 oocyte retrievals were required to conclude MILDA compared to MILDF which was concluded following a single oocyte retrieval (P-value<0.001). Cancellation-rate was significantly lower in the MILDA compared to MILDF group (0% vs 18.93%, P-value <0.001). A higher proportion of top quality embryos were transferred in the MILDA group (66.58% vs 43.67%, P-value<0.001). The MILDA group presented with higher positive-HCG (27.89% vs 23.30%, P-value=0.302), clinical-pregnancy (22.11% vs 17.96%, P-value=0.316) and live-birth rates (16.84% vs 14.08%, P-value=0.487). However, these differences were not significant. Comparing MILDA and NATA groups, the MILDA presented with a lower number of required oocyte retrievals and a higher number of oocytes per oocyte retrieval compared with NATA (3.90±1.56 vs 7.15±1.80; 1.95±0.74 vs 0.89±0.20, P-value<0.001). Moreover, the MILDA presented with a higher mean number of resulting embryos (5.20±0.78 vs 4.82±0.88, P-value<0.001). No difference was observed regarding the proportion of the resulting top quality embryos. The MILDA group presented with slightly higher clinical-pregnancy (22.11% vs 20.09%, P-value=0.628) and live-birth (16.84% vs 14.02%, P-value=0.490) rates, however these differences were not significant. Limitations, reasons for caution The retrospective nature of the study constitutes a major limitation. Considering that numerous confounders are inevitable when retrospective data is analyzed, authors employed strict eligibility criteria in an effort to reduce bias. Statistical analysis revealed a well-controlled population, considering that general patients’ characteristics did not differ between the three groups. Wider implications of the findings: Embryo accumulation may constitute an efficient management strategy for POR, as more embryos of better quality are available for ET compared to fresh-IVF-ET. Mild stimulation should be preferred for embryo accumulation instead of natural cycles, as less oocyte retrievals are required. Future studies should be conducted to verify these conclusions. Trial registration number Not applicable

A flexible short protocol in women with poor ovarian response over 40 years old

Background Ovarian responsiveness to controlled ovarian stimulation is essential for a successful clinical outcome in assisted reproductive technology (ART) cycles. We aimed to find a suitable new ovulation stimulation protocol for poor ovarian response (POR) patients over 40 years old. Methods A retrospective analysis of 488 ART cycles was evaluated from January 2015 to June 2019. Comparisons were made between the flexible short protocol (FSP), routine short protocol and mild stimulation protocol. Results Compared with the routine short protocol, the FSP delayed the gonadotropin start time and reduced the total gonadotropin dose per stimulation cycle. At the same time, compared with the mild stimulation protocol, the FSP improved oocyte quality and embryo quality and improved embryo implantation potential after transfer. Furthermore, the use of the FSP reduced the probability of premature ovulation, as it inhibited the premature luteinizing hormone (LH) surge to a certain extent. Conclusions The FSP yielded better outcomes than other protocols for patients with POR over 40 years old in our study. However, further prospective studies are needed to provide more substantial evidence and to determine whether the FSP can be successful for both patients over 40 years group and younger POR patients.

Mild stimulation should be mandatory for oocyte donation

ABSTRACT The increasing commercialization of oocyte donation is a source of concern. This evolution is expressed in the fact that oocyte donors’ interests are not a priority. For decades now, people mention that oocyte donation holds serious health risks for donors, as if this is an unavoidable given. However, most of the harm is caused by high hormonal stimulation. The risk/benefit balance of high stimulation compared to the risk/benefit balance of mild stimulation does not justify causing greater harm to donors, especially given the fact that donors submit to the procedure without any medical benefit for themselves and to help others.