Progesterone after mifepristone: A pilot prospective single arm clinical trial for women who have changed their mind after commencing medical abortion.

AIM: This pilot study aimed to assess the utility of an oral progesterone treatment protocol for women who commenced medical abortion and then changed their mind and wished instead to maintain their pregnancy. METHODS: The Progesterone-After-Mifepristone-pilot for efficacy and reproducibility (PAMper) trial was designed as a prospective single-arm pilot clinical trial, conducted via telehealth. Women aged 18 to 45 years in Australia who reported ingesting mifepristone within the last 72 h to initiate medical abortion and had not taken misoprostol were included. Initial contact was by a web-based form. Following informed consent, participants were prescribed oral progesterone to be taken 400 mg twice per day for 3 days then 400 mg at night until completion of a 19 day course. Pregnancy viability was assessed by ultrasound scan after 14 days of progesterone treatment. RESULTS: Between October 2020 and June 2021, nine women contacted the PAMper trial, of whom six enrolled and commenced progesterone treatment. These women reported ingesting mifepristone at 40-70 days of gestation, with progesterone being commenced within 5.7-72 h of mifepristone ingestion. Five participants had ongoing, live pregnancies at the primary endpoint (ultrasound at >2 weeks). One participant had a miscarriage after 9 days of progesterone treatment. There were no clinically significant adverse events. CONCLUSION: This small study demonstrated a clinically sound protocol for researching the use of progesterone-after-mifepristone for women in this circumstance. Results of this pilot study support the need for further larger scale trials in this field.

Relationship Between Steroid Hormone Profile and Premenstrual Syndrome in Women Consulting for Infertility or Recurrent Miscarriage.

To determine the relationships between luteal-phase steroidal hormonal profile and PMS for a large number of women attending a dedicated fertility clinic. This was a retrospective cross-sectional study on women attending a hospital-based clinic for fertility concerns and/or recurrent miscarriage. All participants were assessed with a women's health questionnaire which also included evaluation of premenstrual symptoms. Day of ovulation was identified based on the peak mucus symptom assessed by the woman after instruction in a fertility awareness-based method (FABM). This enabled reliable timing of luteal-phase serum hormone levels to be taken and analysed. Between 2011 and 2021, 894 of the 2666 women undertaking the women's health assessment had at least one evaluable serum luteal hormone test. Serum progesterone levels were up to 10 nmol/L lower for symptomatic women compared with asymptomatic women. This difference was statistically significant (p < 0.05) for the majority of PMS symptoms at ≥ 9 days after the peak mucus symptom. A similar trend was observed for oestradiol but differences were generally not statistically significant. ROC curves demonstrated that steroid levels during the luteal phase were not discriminating in identifying the presence of PMS symptoms. Blood levels for progesterone were lower throughout the luteal phase in women with PMS, with the greatest effect seen late in the luteal phase.

Fertility awareness education improves fertility cycle knowledge and may reduce time-to-pregnancy in subfertile women.

Research suggests that low fertility awareness (FA) may be a contributing factor to infertility. The aim of this study was to determine whether education improves knowledge in FA and to explore the associations between FA knowledge and time to pregnancy (TTP). A 20-point self-administered FA questionnaire (FAQ) was completed by 180 subfertile women on their first visit to a hospital-based fertility assessment and research clinic, followed by an education session on FA. Women completed the same FAQ after receiving the education session. There was an increase in the FAQ score after the women received FA education (post-education FAQ score: mean, M = 15.68, SD = 1.8) compared with the score before the session [(pre-education FAQ score: M = 13.87, SD = 1.9), t(179)=-10.547, p < 0.001]. Pregnancy was achieved in 88 women (49%). Women with a higher post-education FAQ score (≥15 points) had a shorter TTP (M = 6.4 months, SD = 4.1) than women with post-education FAQ scores <15 [M = 8.8 months, SD = 6.0, t(86)=2.231, p = 0.028]. Greater time trying to conceive was negatively predictive of the hazard for achieving a pregnancy (b=-0.021, se = 0.008, p = 0.005), while age had no significant effect. FA knowledge in women attending a fertility clinic significantly improved after education. Higher FA may reduce TTP in subfertile women who are actively trying to conceive naturally.

Progesterone for women with threatened miscarriage (STOP trial): a placebo-controlled randomized clinical trial.

STUDY QUESTION: In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? SUMMARY ANSWER: In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates. WHAT IS KNOWN ALREADY: Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit. STUDY DESIGN, SIZE, DURATION: We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: This trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group. MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes. LIMITATIONS, REASONS FOR CAUTION: Our study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis. WIDER IMPLICATIONS OF THE FINDINGS: We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research. STUDY FUNDING/COMPETING INTEREST(S): Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. TRIAL REGISTRATION NUMBER: ACTRN12611000405910. TRIAL REGISTRATION DATE: 19 April 2011. DATE OF FIRST PATIENT'S ENROLMENT: 06 February 2012.

Improved laparoscopic skills in gynaecology trainees following a simulation-training program using take-home box trainers.

BACKGROUND: Lack of time and access to equipment are recognised barriers to simulation training. AIM: To investigate the effect of a take-home laparoscopic simulator training program on the laparoscopic skills of gynaecology trainees. METHOD: Participants (n = 17 in 2015, n = 16 in 2016) were supplied with a box trainer, associated equipment and instructions on self-directed training. A program was designed and implemented in 2015 comprising of ten weekly laparoscopic skills tasks and modified in 2016 to eight monthly tasks. Half of the participants were randomly allocated a supervisor. Participants performed baseline and post-training assessments of laparoscopic skills in a box trainer task (thread transfer) and virtual reality simulator tasks (laparoscopic tubal ligation and bilateral oophorectomy). RESULTS: Trainees in 2015 demonstrated an improvement in the median time to complete the laparoscopic tubal ligation task (baseline 124 s vs post-training 91 s, P = 0.041). There was no difference in the number of tubal ligation bleeding incidents, or in the time taken to complete the box trainer thread transfer task. In 2016 trainees demonstrated improvement in tubal ligation time (baseline 251 vs 71 post-training, P = 0.021) and bilateral oophorectomy time (baseline 891 s vs 504 post-training, P = 0.025). There was no significant difference in other outcome measures. There was no difference found in performance when groups were compared by supervisor allocation. CONCLUSION: A take-home box trainer simulation-training program was associated with improvement in laparoscopic skills. This type of program may improve trainee access to simulation training.

Bioethical and Moral Perspectives in Human Reproductive Medicine.

A reductive reading of Humanae vitae seeks to limit its appeal to a ban on contraception. In truth, however, it offers a vision of human sexuality and conjugal love with broad and enduring relevance. In setting forth the intrinsic complementarity and irreducibility of the unitive and procreative dimensions of the conjugal act, Paul VI has given us a hermeneutical key for assessing many contemporary ethical dilemmas in human reproductive medicine. From this perspective, this article seeks to apply the logic of Humanae vitae to several real-life scenarios confronted by medical practitioners, educators, and ethicists working in the field of fertility and reproductive health. These include a consideration of the ethics of prescribing hormonal contraceptives, the possibilities of investigating male infertility, issues of cooperation in counseling and assisting conception in same-sex relationships, the ethics pertaining to assisted reproductive technology (ART), the contested case of prenatal adoption, and the application of double-effect reasoning. SUMMARY: On the occasion of the fiftieth anniversary of the promulgation of Pope Paul VI's encyclical Humanae vitae, this article seeks to defend its enduring relevance to modern-day society, through application of its reasoning to contemporary dilemmas in reproductive medicine. It considers real cases of the ethics of prescribing hormonal contraceptives, of investigating male infertility, of cooperating in counseling and assisting conception in same-sex relationships, of ART, of prenatal adoption, and the application of double-effect reasoning.