The role of mifepristone on first trimester miscarriage treatment - A double-blind randomized controlled trial - MiFirsT.

OBJECTIVES: To evaluate the efficacy of combined mifepristone and misoprostol compared to misoprostol alone in outpatient medical treatment of first trimester miscarriage. Additionally, the study intends to compare the rate of complications, adverse effects, and treatment acceptability between groups. STUDY DESIGN: Single-center double-blind randomized placebo-controlled trial including women with diagnosis of missed first trimester miscarriage up to 9 weeks of gestation. RESULTS: Between April 2019 and November 2021, 216 women diagnosed with first trimester miscarriage up to 9 weeks of gestation were randomly assigned to mifepristone group or to misoprostol-alone group. Data from 105 women in mifepristone group and 103 women in misoprostol-alone group were analyzed, with no differences in baseline characteristics. The median time between medications (oral mifepristone/placebo and vaginal misoprostol) was nearly 43 h in both groups (p = 0.906). The median time to first follow-up was 2.6 weeks (IQR 1.0) in mifepristone group and 2.4 weeks (IQR 1.0) in misoprostol-alone group (p = 0.855). The overall success rate of medical treatment was significantly higher in the mifepristone-group comparing to misoprostol-alone group (94.3% vs. 82.5%, RR 1.14, 95% CI, 1.03-1.26; p = 0.008). Accordingly, the rate of surgical treatment was significantly lower in the mifepristone-group (5.7% vs.14.6%, RR 0.39, 95% CI, 0.16-0.97; p = 0.034). The composite complication rate was similar and lower than 4% in both groups. No case of complicated pelvic infection, hemodynamic instability or inpatient supportive treatment was reported. There were no significant differences in the rates of adverse events, median score for vaginal bleeding intensity or analgesics use. Despite the same median value, the score of abdominal pain intensity was significantly higher in the mifepristone-group (p = 0.011). In both groups, more than 65% of the women classified the treatment as "good" and 92% would recommend it to a friend on the same clinical situation. CONCLUSION: The mifepristone plus vaginal misoprostol combined treatment for medical resolution of first trimester miscarriage resulted in significant higher success rate and lower rate of surgical uterine evacuation comparing to misoprostol-alone treatment, with no relevant differences in adverse events or treatment acceptability.

Shared IVF among female couples: clinical outcomes of the Reception of Oocytes from the Partner (ROPA) method.

RESEARCH QUESTION: What is the population undergoing the ROPA (Reception of Oocytes from Partner) method and what are the outcomes of the technique? DESIGN: Case series of all ROPA treatments carried out between 2011 and 2020 in 18 fertility clinics in Spain. Demographic characteristics, cycle features, laboratory and clinical outcomes, and the intentions regarding the disposition of surplus embryos were analysed. RESULTS: Donor patients were on average 3.5 years younger than recipients (P = 0.001). No significant differences were found in body mass index or anti-Müllerian hormone. In 13% of cases, fertility issues were found: poor ovarian reserve (6.8%); endometriosis (2.9%); and polycystic ovary syndrome (2.2%). Including cases of advanced age (38 years old or older), more than one-half of couples (53.6%) had some condition that could affect fertility. Mean number of mature oocytes per cycle was 10 (+/- 5.7), and fertilization rate was 74.5% (+/- 18.8). Mean number of viable embryos was 3.2 (+/- 1.5). Surplus embryos were cryopreserved in 50.4% of cycles. Outcomes after embryo transfers from ROPA, and subsequent frozen cycles were as follows: positive pregnancy test (61.0%), clinical pregnancy (54.1%) and miscarriage rate (16.1%). Other outcomes were live birth rate per embryo transfer (44.7%); multiple pregnancy rate (5.4%); per cumulative ROPA cycle (48.6%); and per couple (61.6%). CONCLUSION: The outcomes of the ROPA method are reassuring. About one-half of the ROPA cycles resulted in a live birth and one-quarter of the cycles had surplus embryos after achieving a live birth. Main neonatal outcomes were also reassuring.

Female couples undergoing assisted reproduction - choices and the importance of pregnancy and genetics.

OBJECTIVE: To evaluate female couples' reproductive choices, the importance given to genetics and pregnancy and their expectations regarding mother-child relationship. METHODS: Observational study based on an anonymous survey applied to 217 patients during 2021. The survey was given to female couples under reproductive treatment in a private fertility clinic. The outcomes were divided into 3 main groups: the choice of their reproductive treatment, motherhood and biological links, and their plans for future reproductive treatments. RESULTS: Most patients found it easy to choose their treatments and roles. The choice was mainly driven by success rates, costs, and simplicity, except for ROPA for which sharing biological motherhood was the main reason. Most couples consider genetics and pregnancy important but, in the end, they believe they will have a similar connection to their child, regardless of the role played. In the future, some couples consider doing the same treatment while others consider inverting roles. CONCLUSIONS: Most female couples have no difficulty when it comes to choosing a reproductive treatment or role to play, mainly based on costs, success rates and the possibility of sharing biological motherhood with the ROPA method. These patients give great importance to genetics and pregnancy, but they expect a similar connection to their child regardless of the type of treatment and the roles played.

Similar reproductive outcomes between lesbian-shared IVF (ROPA) and IVF with autologous oocytes.

PURPOSE: To compare reproductive outcomes of the ROPA method (reception of oocytes from partner) to IVF with autologous oocytes. To study the impact of the absence of a genetic link between the embryo and its recipient in reproductive outcomes. METHODS: Retrospective multicentric cohort study performed from January 2011 to December 2020 in 18 fertility clinics in Spain. A total of 99 ROPA (73 couples) and 2929 non-ROPA cycles (2334 couples or single patients) of women younger than 38 years old with no known female fertility disorder were included. Clinical outcomes were compared between both groups and included positive pregnancy test, clinical pregnancy, miscarriage, ectopic pregnancy, pre-term birth, live birth, weeks of gestation at birth, and newborn weight at birth. RESULTS: No differences were found between groups in clinical outcomes. The total clinical pregnancy rates per embryo transfer were 57% and 50.2% (p = 0.15) and the live-birth rates were 46.1% and 40.9% (p = 0.14) for the ROPA and non-ROPA groups, respectively. When adjusted to age and BMI of donors and recipients, there were also no differences in live-birth rates between both groups. The cumulative live-birth rate per ROPA cycle was 73.7% and the cumulative live-birth rate per couple was 78.3%. CONCLUSION: Clinical outcomes following the ROPA method and IVF with autologous oocytes were found to be similar. These findings suggest no impact of the absence of genetic ties between the embryo and the uterus on reproductive treatments' outcomes. Data regarding the outcomes of the ROPA method are reassuring.

ROPA - Lesbian shared in vitro fertilization - Ethical aspects.

Recently, a technique of assisted reproduction was developed to allow lesbian women to share biological motherhood of their offspring - the ROPA method (in Spanish - Recepción de Ovocitos de Pareja; in English - Reception of Partner's Oocytes), also known as lesbian shared in vitro fertilization. One mother provides the oocytes (genetic mother) and the other receives the embryo and gets pregnant (gestational mother). As for most issues related to medically assisted reproduction, this technique raises a lot of ethical questions in respect to patients, future offspring, gametes, and embryos. Furthermore, the fact that it is directed to homosexual women poses its own issues, both biological and social in nature. This is a state-of-the-art review of the main ethical dilemmas related to this technique, primarily focusing on the basic principles of bioethics, but also specific concerns directly related to this kind of treatments.

Development of a birthweight standard and comparison with currently used standards. What is a 10th centile?

INTRODUCTION: Fetal growth charts are often used in clinical practice. It is important to understand the usefulness and the pitfalls associated with these tools. Without validation, it is difficult to ascertain if the cutoffs we intend are the ones we actually select. We developed a national standard for birthweight (BW) and compared it with other published reference values. STUDY DESIGN: Multicenter retrospective study. We collected data on live births, including first trimester ultrasound and pathology, from 23 to 42 weeks' gestational age (GA). We used a variation of the lambda (λ), mu (µ), and sigma (σ) method (LMS) to construct and smooth predicted centiles. GA data was plotted and modeled in days from 24 to 42 weeks. Resulting centiles were validated and compared with other published and widely used reference values. Data from both BW and estimated fetal weight was used to validate the model. RESULTS: Data on 661,338 births were collected from 22 institutions, including 71,515 cases with first trimester ultrasound. We excluded preterm cesarean section from analysis, because of a significant bias (up to 18%) on BW and used exclusively first trimester ultrasound dates from 34 to 42 weeks. The standard compares favorably with tables currently in use, both ultrasound and birthweight based. CONCLUSION: The use of first trimester ultrasound limits variability by minimizing some random error sources, such as data introduction and GA errors, while allowing better precision (GA in days). This results in a narrower range in the extreme centiles than other charts. Validation with estimates of fetal weight are sound in second and early third trimester fetuses, because that will be a "real world" usage of this standard. While there are similarities between our series and some international/foreign growth charts, other are unfit to characterize our population. This reinforces the need for validation of standards, and sound methodological practices when doing so.

Gestational age and fetal growth assessment among obstetricians.

OBJECTIVE: We aimed to characterize gestational age assessment and fetal growth evaluation among obstetricians. METHODS: Observational, cross-sectional study. We applied a questionnaire to obstetrics specialists and residents, during a national congress on obstetrics. RESULTS: Almost all 179 respondents correct gestational age in the first trimester by ultrasound, but 63% only if there is a difference of 2-9 days. Ultrasound at 11-13 weeks was considered more accurate than at 8-10 weeks by 81%, with a higher proportion of specialists choosing correctly the last answer (p = 0.05). One-third of the respondents did not correctly point the error associated with the ultrasound estimation of fetal weight (EFW). Of the 88% who use a growth table, only 32% were able to identify it by publication/author. Ninety-eight percent identify fetal growth restriction risk (FGR) with centiles (10th in 76%) and 73% of doctors diagnose FGR without other pathological findings (10th in 49%). 44% finds that a low EFW centile maintenance (4th to 3rd) is more worrisome than the crossing of two quartiles (75th to 24th). CONCLUSIONS: The role of ultrasound in gestational age assessment and use of EFW use for FGR classification was disparate among participants. EFW and respective centiles may be over relied upon.