Search

Embryo implantation failure is a major cause of infertility in women of reproductive age and a better understanding of uterine factors that regulate implantation is required for developing effective treatments for female infertility. This study investigated the role of the uterine kisspeptin receptor (KISS1R) in the molecular regulation of implantation in a mouse model. To conduct this study, a conditional uterine knockout (KO) of Kiss1r was created using the Pgr-Cre (progesterone receptor-CRE recombinase) driver. Reproductive profiling revealed that while KO females exhibited normal ovarian function and mated successfully to stud males, they exhibited significantly fewer implantation sites, reduced litter size and increased neonatal mortality demonstrating that uterine KISS1R is required for embryo implantation and a healthy pregnancy. Strikingly, in the uterus of Kiss1r KO mice on day 4 (D4) of pregnancy, the day of embryo implantation, KO females exhibited aberrantly elevated epithelial ERα (estrogen receptor α) transcriptional activity. This led to the temporal misexpression of several epithelial genes [Cftr (Cystic fibrosis transmembrane conductance regulator), Aqp5 (aquaporin 5), Aqp8 (aquaporin 8) and Cldn7 (claudin 7)] that mediate luminal fluid secretion and luminal opening. As a result, on D4 of pregnancy, the lumen remained open disrupting the final acquisition of endometrial receptivity and likely accounting for the reduction in implantation events. Our data clearly show that uterine KISS1R negatively regulates ERα signaling at the time of implantation, in part by inhibiting ERα overexpression and preventing detrimentally high ERα activity. To date, there are no reports on the regulation of ERα by KISS1R; therefore, this study has uncovered an important and powerful regulator of uterine ERα during early pregnancy., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This study investigated the efficacy of GnRH agonists concomitantly with transient aromatase inhibitor and tranexamic acid to treat women with uterine arteriovenous malformations (AVMs) associated with abnormal uterine bleeding (AUB) to preserve fertility and determine reproductive outcome., Methods: This was a prospective cohort study in a tertiary centre. Doppler ultrasound demonstrated AVM in 19 women with AUB 1-28 weeks following spontaneous or therapeutic abortion and in one woman 4 years after normal pregnancy while taking an oral contraceptive. On the basis of experience from the first three cases, 17 women were treated with tranexamic acid (1 g three times daily orally for 5 days), a GnRH agonist (3.75-11.25 mg, for 1-3 months), plus an aromatase inhibitor (letrozole 2.5 mg once daily for 5days) with the initial injection of GnRH agonist. Two women required blood transfusion, and one required uterine tamponade with Foley catheter balloon in the first 48 hours to control heavy bleeding (Canadian Task Force Classification II-2)., Results: All 20 AVMs resolved within 1-3 months of treatment. Of 16 women who attempted pregnancy, all (100%), including two who had uterine artery embolization (one after hysteroscopic septoplasty), conceived spontaneously with 18 live births. Two women are using contraception (one taking an oral contraceptive, one using a levonorgestrel intrauterine system), and one 40-year-old is not using contraception. One woman had hysteroscopic endometrial ablation followed by vaginal hysterectomy for AUB at 1 and 2 years later., Conclusion: A GnRH agonist in combination with transient aromatase inhibitor and tranexamic acid is an effective management strategy to treat and maintain reproduction in women with AVMs associated with AUB., (Copyright © 2018 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1(-/-) mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r(-/-) mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence.

Background and Objectives: Although uterine stenting is performed routinely following hysteroscopic metroplasty, we were unable to find any evidence documenting its value with regards to septum reformation and/or obstetrical performance. To evaluate the benefits of intrauterine Foley catheter/balloon splinting after resectoscopic septum division on septum reformation, fertility, and pregnancy outcomes., Design and Setting: Prospective, randomized controlled pilot study (Canadian Task Force Classification I) conducted in university affiliated teaching hospital., Patients and Methods: Twenty-eight women with infertility and/or adverse pregnancy outcomes diagnosed with intrauterine septum were randomized into having a No. 14 pediatric Foley catheter/balloon for 5 days (n=13) vs. no balloon (n=15) following resectoscopic septum division. None of the patients received preoperative endometrial thinning, antibiotic prophylaxis or adjuvant postoperative hormone therapy. All uterine septa were divided under general anaesthesia using a 26 F (9 mm) resectoscope with a monopolar electrical knife using glycine irrigant solution (1.5%) and 120 watts of power of low voltage (cut) waveform., Results: The median age (range) was 29 years (23-38) and 32 years (22-40), respectively (P=.59). The groups were comparable by age, past obstetrical performance and comorbidities including endometriosis stage I-IV in 3 and 4 women, in the catheter/balloon and balloon group, respectively, and one in each group of polycystic ovarian syndrome and Crohn disease and one case of tubal obstruction in the balloon group. There were no intra- or postoperative complications. At 3 months, a hysterosalpingogram was done in 10 (77%) and 13 (87%) women, respectively, the results of which were normal. At 12-18 months, 1 woman in the balloon and 3 in the control group were not trying to conceive and 1 in each group had not conceived. Of the remaining women, 11 (92%) in each group had conceived and pregnancy outcomes included spontaneous abortion 3 (25%) and 4 (33.3%), ectopic pregnancy 0 and 1, second trimester loss 1 (8.3%) and 0 and term pregnancy 8 (66.6%) in both groups. Conception through assisted reproductive technology occurred in 2 and 1 woman, respectively., Conclusions: Following resectoscopic septum division with monopolar knife electrode, splinting the uterine cavity with Foley catheter provided no advantage in septum reformation, clinical pregnancy rate, and pregnancy outcomes.