Hormone therapy for uterine and endometrial development in women with premature ovarian insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear. OBJECTIVES: To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2021. We also checked references of included studies, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating the effect of various hormonal preparations on the uterine development of women diagnosed with POI. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was uterine volume; secondary outcomes were endometrial thickness, endometrial histology, uterine perfusion, reproductive outcomes, and any reported adverse events. MAIN RESULTS: We included three studies (52 participants analysed in total) investigating the role of various hormonal preparations in three different contexts, which deemed meta-analysis unfeasible. We found very low-certainty evidence; the main limitation was very serious imprecision due to small sample size. Conjugated oral oestrogens versus transdermal 17ß-oestradiol We are uncertain of the effect of conjugated oral oestrogens compared to transdermal 17ß-oestradiol (mean difference (MD) -18.2 (mL), 95% confidence interval (CI) -23.18 to -13.22; 1 RCT, N = 12; very low-certainty evidence) on uterine volume, measured after 12 months of treatment. The study reported no other relevant outcomes (including adverse events). Low versus high 17ß-oestradiol dose We are uncertain of the effect of a lower dose of 17ß-oestradiol compared to a higher dose of 17ß-oestradiol on uterine volume after three or five years of treatment, or adverse events (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes. Oral versus vaginal administration of oestradiol and dydrogesterone We are uncertain of the effect of an oral or vaginal administration route on uterine volume and endometrial thickness after 14 or 21 days of administration (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes (including adverse events). AUTHORS' CONCLUSIONS: No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI.

Implantation in the lower half of the uterine cavity and decreased trophoblastic thickness can predict subsequent miscarriage: a prospective cohort study.

Abstract: Embryo implantation is vital for successful conception but remains to be fully understood. Trophoblast invasion is key for implantation, with anchorage and depth of placentation determined by its extent. There is a dearth of synchronous information regarding IVF, implantation site, and trophoblastic thickness (TT). Our aim was to determine whether pregnancy implantation site and TT, had an impact on outcomes of IVF pregnancies. This prospective observational study was undertaken at a tertiary referral UK fertility unit over 14 months, collecting data on implantation site and TT from three-dimensional (3D) images of the uterus following early pregnancy scan. Of the 300 women recruited, 277 (92%) had live births, 20 (7%) miscarried, 2 (0.7%) had stillbirths, and 1 (0.3%) had a termination. Significantly more pregnancies that resulted in miscarriage (7/20, 35%) were located in the lower uterine cavity when compared to ongoing pregnancies (15/277, 5%) (P < 0.01). TT was significantly higher in ongoing pregnancies when compared with those who miscarried (7.2 mm vs 5.5 mm; P < 0.01). Implantation in the lower half of the uterine cavity and decreased TT are significantly associated with an increased rate of miscarriage. Identification of those at risk should prompt increased monitoring with the aim of supporting these pregnancies. Lay summary: Implantation of an embryo in the womb is vital for a successful pregnancy. We wanted to find out whether findings on an ultrasound scan in early pregnancy had an impact on outcomes of IVF pregnancies. Three hundred women were recruited to the study, 277 (92%) had live births and unfortunately 20 (7%) had a miscarriage, 2 (0.7%) had stillbirths, and 1 (0.3%) had a termination. Many more of the pregnancies that miscarried implanted in the lower part of the womb. The thickness of the infiltration of the pregnancy into the womb was significantly higher in the ongoing pregnancies. We concluded that implantation in the lower half of the womb and reduced infiltration of the pregnancy seen on scan are associated with an increased rate of miscarriage. We propose that when we identify those at risk, we should increase monitoring, with the aim of supporting these pregnancies.

Emergency intrauterine device insertion in teenagers: an informal retrospective study.

BACKGROUND: Widespread and increased availability of oral emergency contraception (EC) over the past 10 years has made little difference to rates of unintended pregnancy, abortion and repeat abortion amongst teenagers. The insertion of an intrauterine device for EC (EC-IUD) is 98-99% effective compared with 85% for oral methods and can be used for ongoing, long-term reversible contraception. However this method is seldom used for teenagers, a group with a high risk of unintended pregnancy, and there is little published data on the use of EC-IUD in this group. METHODS: An anonymous case note review of EC-IUD use in teenagers in three centres in the UK was conducted to quantify provision, to identify insertion difficulties and short-term complications and to ascertain compliance with national guidance concerning sexually transmitted infection (STI) risk assessment and prophylaxis. RESULTS: A total of 103 cases was identified over 4 years (2007-2010) from the three centres (London, Liverpool and Aberdeen). The results show that the majority of fittings were straightforward (94%) with few complications. Antibiotic prophylaxis was deemed necessary in 64% of attenders. CONCLUSIONS: The authors recommend that with STI screening and appropriate antibiotic prophylaxis, use of IUDs in women under the age of 20 years should be unrestricted both for long-term contraception and for EC.