The use of propensity score matching to assess the benefit of the endometrial receptivity analysis in frozen embryo transfers.

OBJECTIVE: To study the impact of the endometrial receptivity analysis (ERA) on live birth rates in frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: A single, large, university-affiliated infertility practice. PATIENT(S): Autologous FET cycles between January 1, 2014, and June 30, 2019, were reviewed. Multiple covariates that impact outcomes were used for propensity score matching; 133 ERA patients were matched to 353 non-ERA patients. Patients were assigned to the ERA group if they had an ERA during treatment and underwent at least one "personalized" FET based on the ERA recommendations. INTERVENTION(S): No interventions administered. MAIN OUTCOME MEASURE(S): Live birth rates per cycle in the FET cycle after ERA compared with that of matched non-ERA patients. RESULT(S): The live birth rates for the ERA group, 49.62%, and the matched non-ERA group, 54.96%, (odds ratio 0.8074; 95% confidence interval, 0.5424-1.2018) were not significantly different, nor was a difference seen in subanalyses based on prior number of FETs or receptivity status. CONCLUSION(S): The ERA identifies a patient's putative window of implantation with the goal of improving synchrony with the embryo, thereby achieving higher live birth rates. This study used propensity score matching to control for multiple covariates in a heterogenous group of patients to compare live birth rates. There was no difference in the live birth rate in patients who underwent the ERA compared with that of those who did not.

Does progesterone supplementation improve pregnancy rates in clomiphene citrate and intrauterine insemination treatment cycles?

AIM: To investigate the effect of empiric use of luteal phase progesterone supplementation to improve endometrial receptivity in women undergoing treatment with clomiphene citrate in combination with intrauterine insemination (CC-IUI). DESIGN: Retrospective cohort analysis. SETTING: University fertility center. PATIENTS: 426 CC-IUI cycles from 292 patients with unexplained infertility. INTERVENTIONS: Patients were treated with micronized intravaginal progesterone 100 mg twice daily beginning approximately three days after CC-IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy per initiated cycle as defined by presence of fetal heart rate on ultrasound. RESULTS: Clinical pregnancy rate was higher in patients receiving luteal phase support compared to patients not receiving luteal phase support (odds ratio: 2.04; 95% confidence interval: 1.01-4.14) after adjusting for all factors in the analysis using a multivariate logistic regression model. Age at the start of the cycle, BMI and CC dose were not shown to have an effect on clinical pregnancy rates. Patients with endometrial lining (EML) thickness 6-8 mm and >8 mm had increased clinical pregnancy rates compared to EML <6 mm independent of luteal phase progesterone use. Patients who appear to receive the greatest benefit of progesterone supplementation are in the 6-8 mm EML cohort. CONCLUSIONS: Luteal phase progesterone supplementation in CC-IUI cycles can improve endometrial receptivity as judged by the improved clinical pregnancy rates as the primary outcome.

Role of nuclear progesterone receptor isoforms in uterine pathophysiology.

BACKGROUND: Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function. METHODS: Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed. RESULTS: Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key cellular signaling pathways required for growth. In contrast, progesterone via PR activation appears to increase leiomyoma growth. The exact role of PRs in cervical cancer is unclear. PRs regulate implantation and therefore aberrant PR function may be implicated in recurrent pregnancy loss (RPL). PRs likely regulate key immunogenic factors involved in RPL. However, the exact role of PRs in the pathophysiology of RPL and the use of progesterone for therapeutic benefit remains uncertain. CONCLUSIONS: PRs are key mediators of progesterone action in uterine tissues and are essential for normal uterine function. Aberrant PR function (due to abnormal expression and/or function) is a major cause of uterine pathophysiology. Further investigation of the underlying mechanisms of PR isoform action in the uterus is required, as this knowledge will afford the opportunity to create progestin/PR-based therapeutics to treat various uterine pathologies.

Misperception of estrogen activity in patients treated with an estrogen receptor antagonist.

Measurement of estradiol is an important marker of ovarian function. At low levels, accurate measurement has been difficult because of unique characteristics of immunoassay kits. We present this case to emphasize the importance of accurate estimation of estrogen activity and estradiol levels to avoid unnecessary surgical intervention.

Accessory and cavitated uterine mass with functional endometrium in an adolescent: diagnosis and laparoscopic excision technique.

STUDY OBJECTIVE: Accessory and cavitated uterine masses (ACUM) with functional endometrium can be treated successfully with laparoscopic excision. The objectives of this report are to illustrate the surgical technique used for the removal of this uterine wall mass and to discuss the patient's clinical course and outcomes. DESIGN: Surgical technique and description of 1 case. SETTING: Department of Obstetrics and Gynecology, University Hospitals Case Medical Center. PARTICIPANT(S): A 16-year-old adolescent presented with severe dysmenorrhea and pelvic pain. Ultrasonographic examination and MRI demonstrated a cystic uterine wall mass distinct from the endometrial cavity. INTERVENTION(S): Laparoscopic excision of uterine mass. RESULTS: Pathologic examination of the mass was consistent with an accessory and cavitated uterine mass. A 9-month follow-up after surgical excision of the mass confirmed complete symptom resolution. CONCLUSIONS: ACUM is a unique and not uncommon pathologic category in the adolescent and young adult population. It is associated with severe and intractable dysmenorrhea and pelvic pain. Laparoscopic excision of these masses is justifiable, safe and feasible.

Diagnosis and management of endometrial hyperplasia.

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods.