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PurposeTo provide a comprehensive review of uterus transplantation in 2021, including a discussion of pregnancy outcomes of all reported births to date, the donor and recipient selection process, the organ procurement and transplant surgeries, reported complications, postoperative monitoring, preimplantation preparation, and ethical considerations.MethodsLiterature review and expert commentary.ResultsReports of thirty-one live births following uterus transplantation have been published from both living and deceased donors. The proper selection of donors and recipients is a labor-intensive process that requires advanced planning. A multidisciplinary team is critical. Reported complications in the recipient include thrombosis, infection, vaginal stricture, antenatal complications, and graft failure. Graft rejection is a common occurrence but rarely leads to graft removal. While most embryo transfers are successful, recurrent implantation failures in uterus transplant patients have been reported. Rates of preterm delivery are high but appear to be declining; more data, including long-term outcome data, is needed.ConclusionsUterus transplantation is an emerging therapy for absolute uterine factor infertility, a condition previously without direct treatment options. It is paramount that reproductive health care providers are familiar with the uterus transplantation process as more patients seek and receive this treatment.

Assisted reproduction is associated with only a slightly increased risk for postpartum mood and anxiety disorders. Findings persist when matching for female infertility and obstetric complications. Asian patients were at a lower risk than their White counterparts for postpartum mood disorder development.

Gynecologic emergencies may result from congenital uterine anomalies (CUAs) with outflow tract obstruction. Not limited to the “classic” presentation of an adolescent amenorrheic pain patient, such anomalies should be part of the differential diagnosis for adult female patients presenting with severe pelvic pain. Obstructed rudimentary noncommunicating cavitary horns may result in severe chronic or acute pain and necessitate urgent surgical management. While two-dimensional (2D) ultrasound is often the initial diagnostic tool, three-dimensional (3D) ultrasound and MRI can accurately delineate CUAs for definitive diagnosis. When excision of a rudimentary horn is required, a laparoscopic approach is preferable. This case series focuses on two adult patients with severe pelvic pain due to unicornuate uteruses with obstructed noncommunicating cavitated rudimentary horns. Both cases involve a delayed diagnosis, the inability to make the diagnosis at standard surgical observation, and the resultant need for urgent surgical management.

Uterus transplantation (UTx) is a rapidly evolving treatment for uterine factor infertility. New centers offering this treatment must decide whether to utilize living donors, deceased donors, or both. Although limiting UTx to deceased donors eliminates the surgical risks for living donors, an adequate supply of suitable deceased uterus donors in the United States is an emerging concern. Previous studies describing the paucity of deceased uterus donors failed to consider key donor characteristics, potentially overestimating the available organ pool. To estimate the United States’ supply of deceased donor uteri; we extrapolated detailed clinical and demographic information from the regional donor datasets available from three organ procurement organizations to the national Organ Procurement and Transplantation Network donor pool. We estimate there are approximately 3700 possible and 400 optimal uterus donors annually in the United States. Given these projections and the number of women with uterine factor infertility in the U.S. who pursue parenthood through alternative strategies, we conclude that, as uterus transplant transitions from research to established clinical care, demand could quickly exceed the deceased donor supply. The liberalization of deceased donor selection criteria may be insufficient to address this imbalance; therefore, fulfilling the anticipated increased demand for uterus transplantation may require and justify greater use of living donors.

PurposeTo determine whether patients with Marfan syndrome are at an increased risk for reproductive disorders.MethodsThis retrospective cohort study was conducted using the US collaborative network on the TriNetX research network of health care organizations. We included female patients aged 18–44 and identified a cohort of 4347 patients with Marfan syndrome (ICD-10 Q87.4). Our control cohort consisted of 16,424,990 patients without a diagnosis of Marfan syndrome or Ehlers-Danlos syndrome (ICD-10 Q79.6). The primary outcomes included gynecologic diagnoses such as dysmenorrhea and endometriosis, and our secondary outcomes included urogynecologic, fertility, and obstetric outcomes, all identified by ICD-10 codes. We conducted a relative risk analysis with a p-value of <0.05 considered significant.ResultsPatients with Marfan syndrome were at an increased risk for pelvic and perineal pain, dysmenorrhea, abnormal uterine bleeding, endometriosis (all p <0.0001), dyspareunia (p =0.0009), leiomyoma (p =0.0076), polyp of female genital tract (p =0.016), urinary incontinence (p <0.0001), female genital prolapse (p =0.0006), fertility testing (p =0.0075), cesarean delivery (p =0.0003), gestational hypertension (p =0.0012), and pre-eclampsia (p =0.0024) compared to the control group following an adjusted, matched comparison.ConclusionsPatients with Marfan syndrome have an increased risk of numerous reproductive disorders and obstetric complications compared to patients without this diagnosis.

PurposeTo compare growth factor and cytokine profiles in the endometrial secretions of patients with and without endometriosis to determine whether a particular protein profile is predictive of the disease.MethodsPatients undergoing laparoscopic gynecologic surgery for benign indications were recruited for this prospective cohort study. Prior to surgery, endometrial fluid was aspirated and multiplex immunoassay was used to quantify 7 cytokines and growth factors. During surgery, each patient was staged according to the ASRM staging system for endometriosis. Cytokines and growth factors were evaluated using the Mann-Whitney and Kruskal-Wallis tests. Combinations of cytokines were evaluated using logistic regression analysis, and ROC curves were generated to evaluate the predictive capacity of the assay.ResultsEndometrial secretions were analyzed from 60 patients. Nineteen had stage 3–4 endometriosis, 19 had stage 1–2 disease, and 22 had no endometriosis. There were no significant differences between controls and stage 1–2 endometriosis; however, levels of IL-1α and IL-6 were significantly increased in women with moderate-to-severe disease. A combination of IL-1α, IL-1β, and IL-6 in endometrial secretions predicts stage 3–4 endometriosis with an AUC of 0.78. A threshold value of 118 pg/mL yields a sensitivity of 75% and specificity of 70%.ConclusionAspiration of endometrial fluid is a safe and effective approach for evaluating the endometrial profile of women with endometriosis. Women with moderate-to-severe endometriosis demonstrate a distinct cytokine profile compared to controls. A combination of IL-1α, IL-1β, and IL-6 in the endometrial secretions is predictive of stage 3–4 endometriosis, but is not predictive of minimal-to-mild disease.

Background/Objective: Fertility preservation is an important part of oncologic care for newly diagnosed gynecologic cancers for reproductive-age women, as many treatment options negatively impact fertility. The goal of this study is to examine factors that influence access to fertility specialists for women with newly diagnosed gynecologic cancer. Methods: This institutional review board approved a retrospective cohort study investigating the impacting factors on the referral rate from gynecologic oncologists (GO) to reproductive endocrinologists and infertility (REI) specialists at a single academic institution between 2010–2022 for patients age 18–41 at diagnosis. Electronic medical records were used to identify demographics and referral patterns. Mixed logistic models were utilized to control cluster effects of the physicians. Results: Of 816 patients reviewed, 410 met the criteria for inclusion. The referral rate for newly diagnosed gynecologic malignancies was 14.6%. Younger patients were more likely to have an REI referral (p < 0.001). The median time from first GO visit to treatment was 18.5 days, and there was no significant difference in those who had REI referrals (p = 0.44). Only 45.6% of patients had fertility desire documented. A total of 42.7% had fertility-sparing treatment offered by a GO. REI referral did not significantly change the time to treatment (p = 0.44). An REI referral was more likely to be placed if that patient had no living children, no past medical history, or if the referring GO was female (OR = 11.46, 6.69, and 3.8, respectively). Conclusions: Fertility preservation counseling is a critical part of comprehensive cancer care; yet, the referral to fertility services remains underutilized in patients with newly diagnosed gynecologic cancer. By demonstrating these biases in REI referral patterns, we can optimize provider education to enhance fertility care coordination.

Uterus transplantation is a surgical treatment for women with congenital or acquired uterine factor infertility. While uterus transplantation is a life-enhancing transplant that is commonly categorized as a vascular composite allograft (e.g., face or hand), it is similar to many solid organ transplants (e.g., kidney) in that both living donors (LDs) and deceased donors (DDs) can be utilized for organ procurement. While many endpoints appear to be similar for LD and DD transplants (including graft survival, time to menses, livebirth rates), there are key medical, technical, ethical, and logistical differences between these modalities. Primary considerations in favor of a LD model include thorough screening of donors, enhanced logistics, and greater donor availability. The primary consideration in favor of a DD model is the lack of physical or psychological harm to a living donor. Other important factors, that may not clearly favor one approach over the other, are important to include in discussions of LD vs. DD models. We favor a stepwise approach to uterus transplantation, one in which programs first begin with DD procurement before attempting LD procurement to maximize successful organ recovery and to minimize potential harms to a living donor.

PurposeTo determine whether differences in birth outcomes among assisted reproductive technology (ART)-treated, subfertile, and fertile women exist in primiparous women with, singleton, vaginal deliveries.MethodsSociety for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to Massachusetts vital records and hospital discharges for deliveries between July 2004 and December 2010. Primiparous women with in-state vaginal deliveries, adequate prenatal care, and singleton birth at ≥ 20 weeks (n = 117,779) were classified as ART-treated (linked to ART data from SART CORS, n = 3138); subfertile (not ART-treated but with indicators of subfertility, n = 1507); or fertile (neither ART-treated nor subfertile, n = 113,134). Outcomes of prematurity (< 37 weeks), low birthweight (< 2500 g), perinatal death (death at ≥ 20 weeks to ≤ 7 days), and maternal prolonged length of hospital stay (LOS > 3 days) were compared using multivariable logistic regression.ResultsCompared to fertile, higher odds were found for prematurity among ART-treated (adjusted odds ratio [AOR] 1.40, 95% confidence interval [CI] 1.25–1.50) and subfertile (AOR 1.25, 95% CI 1.03–1.50) women, low birthweight among ART-treated (AOR 1.41, 95% CI 1.23–1.62) and subfertile (AOR 1.40, 95% CI 1.15–1.71) women, perinatal death among subfertile (AOR 2.64, 95% CI 1.72–4.05), and prolonged LOS among ART-treated (AOR 1.33, 95% CI 1.19–1.48) women. Differences remained despite stratification by young age and absence of pregnancy/delivery complications.ConclusionsGreater odds of prematurity and low birthweight in ART-treated and subfertile, and perinatal death in subfertile deliveries are evident among singleton vaginal deliveries. The data suggest that even low-risk pregnancies to ART-treated and subfertile women be managed for adverse outcomes.

This study describes the characteristics of women who contacted an active program performing uterus transplantation (UTx) in the US, expressing interest in becoming a uterus transplant recipient or a living donor. Basic demographic and self-reported clinical information was collected from women who contacted any of the three US UTx programs from 2015 to July 2022. The three centers received 5194 inquiries about becoming a UTx recipient during the study timeframe. Among those reporting a cause of infertility, almost all of the reports (4066/4331, 94%) were absence of a uterus, either congenitally (794/4066, 20%) or secondary to hysterectomy (3272/4066, 80%). The mean age was 34 years, and 49% (2545/5194) had at least one child at the time of application. The two centers using living donors received 2217 inquiries about becoming living donors. The mean age was 34 years, and 60% (1330/2217) had given birth to ≥1 child. While most of the UTx clinical trial evidence has focused on young women with congenital absence of the uterus, these results show interest from a much broader patient population in terms of age, cause of infertility, and parity. These results raise questions about whether and to what extent the indications and eligibility criteria for UTx should be expanded as the procedure transitions from the experimental phase to being offered as a clinical treatment.