"Can't Touch This!": Laparoscopic management of an obstructed uterus didelphys before and after treatment for pelvic inflammatory disease.

OBJECTIVE: To describe the laparoscopic management of an obstructed uterus didelphys before and after treatment for pelvic inflammatory disease. To compare the appearance of pelvic organs during active infection with their appearance after washout and appropriate antibiotic treatment, emphasizing the importance of knowing when to abort a procedure. DESIGN: Video demonstration of surgical and medical management considerations during a complex pelvic surgery. Visualization of tissue healing that occurs with appropriate antibiotic treatment. SETTING: Academic Center. PATIENT: A patient who presents for definitive surgical management of a uterus didelphys with an obstruction at her right hemicervix. Her presentation is complicated by a tubo-ovarian abscess. INTERVENTION: A uterus didelphys is classically defined as two hemiuteri with duplicated cervices with or without a longitudinal vaginal septum. Uterus didelphys may have an obstruction and/or communication between the two uterine horns, in which case patients may present with complications such as cyclic pelvic pain from hematometra or genital tract infection. This is a case report of a 14-year-old G0 who presented to the emergency department with two weeks of vaginal bleeding, severe diffuse abdominal pain, and malodorous vaginal discharge. Transabdominal ultrasound and a magnetic resonance imaging of the pelvis established a new diagnosis of a uterus didelphys with an obstruction at her right hemicervix and a fistulous tract connecting her right and left hemiuteri at the level of the internal cervical os. She was also found to have a 3 cm left ovarian cyst and a new finding of congenital absence of her right kidney. Patient was administered ceftriaxone, doxycycline, and metronidazole antibiotics as treatment of presumed pelvic inflammatory disease but experienced minimal improvement after 24 hours. The decision was made to proceed with surgical intervention. A survey of the pelvis revealed significant inflammation, friable peritoneum, and endometriosis. The uterine horns in didelphic configurations were visualized. The fimbriae at the left fallopian tube were notably splayed out, swollen, and inflamed. There was a notable large mass in the location where the ovarian cyst had been previously described on imaging. A large amount of purulent material was expressed when compressed, consistent with a tubo-ovarian abscess. The infection likely originated from the menstrual blood collection at the right obstructed cervix that ascended through the communication between the right and left hemiuteri. The pelvis was irrigated thoroughly. At this point, the decision was made to stop the procedure, pursue antibiotic treatment, and resolve the active infection before correcting her complex müllerian anomaly. Patient continued on her antibiotic course, which included piperacillin-tazobactam, while hospitalized, followed by a five-day course of amoxicillin-clavulanate. She was also placed on medroxyprogesterone acetate for menstrual suppression. MAIN OUTCOME MEASURE: Advantage of allowing time for antibiotic treatment and tissue healing before repair of a complex müllerian anomaly. RESULT: With antibiotic treatment, she recovered well postoperatively with resolution of her pain. Three months later, she returned to the operating room for definitive surgical management of her obstructed uterine didelphys. On laparoscopy, there was a significant improvement in tissue quality. Most notably, the fimbriae of the left fallopian tube were no longer inflamed. We proceeded with the planned correction of the complex müllerian anomaly. After resection of the right uterine horn, the fistula tract was identified and also resected. The defect in the right hemicervix was closed over, reinforcing the medial side of the left hemicervix. She had an uncomplicated postoperative recovery, and menses resumed without pain. CONCLUSIONS: The presented case provides unique insight into the tissue healing that occurs before and after antibiotic treatment. Knowing when to stop, especially in the setting of an active infection, is extremely important for performing a procedure safely, minimizing harm, and allowing for robust tissue repair. It is also important to optimize modifiable preoperative factors before correcting a complex müllerian anomaly. Assessing and reassessing the situation during a complex pelvic surgery is essential, especially in the setting of a complex müllerian anomaly where the preoperative examination and imaging may not be definitive.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis.

OBJECTIVE: To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. DESIGN: Retrospective cohort study. SETTING: Donor Egg Bank Database. PATIENTS: Patients undergoing in vitro fertilization using vitrified donor oocytes from 35 in vitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. INTERVENTION: Oocyte donor-recipient cycles. MAIN OUTCOME MEASURES: Ongoing pregnancy rate (OPR) per ET. RESULTS: A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). CONCLUSION: This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

Müllerian Anomalies: Presentation, Diagnosis, and Counseling.

Müllerian anomalies represent a complex collection of developmental defects occurring in up to 5% of the general population. They are increasingly more common in individuals with infertility (8.0%) and in those with a history of pregnancy loss (13.3%); they have the highest prevalence in individuals with a history of both (24.5%). A wide spectrum of anomalies can occur based on the stage at which müllerian development ceases in utero, ranging from mild (eg, a partial uterine septum) to severe, with complete absence of the cervix, uterus, and fallopian tubes (eg, müllerian agenesis). The components of the reproductive tract involved and, importantly, whether an obstruction of the tract is involved correlates with the timing of presentation, the constellation of associated symptoms, and the necessity for either medical or surgical management. Individuals, regardless of the severity of the defect, should be counseled on the gynecologic, reproductive, and obstetric risks associated with their specific müllerian anomaly to minimize adverse sequela and outcomes. We will review the clinical presentation, diagnostic evaluation, and clinical counseling of individuals with müllerian anomalies.

Combining early pregnancy bleeding with ultrasound measurements to assess spontaneous abortion risk among infertile patients.

BACKGROUND: Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood. OBJECTIVE: This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk. STUDY DESIGN: This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate. RESULTS: Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding. CONCLUSION: Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased.

Reproductive surgery: revisiting its origins and role in the modern management of fertility.

For years, reproductive surgery was the mainstay of reproductive care. With the evolution and ultimate success of in vitro fertilization (IVF), reproductive surgery became an adjuvant therapy, indicated mainly for severe symptoms or to enhance success rates with assisted reproductive technologies. As success rates for IVF have plateaued, and emerging data rekindles the enormous benefits of surgically correcting reproductive pathologies, there is renewed interest among reproductive surgeons in reviving research and surgical expertise in this area. In addition, new instrumentation and surgical techniques to preserve fertility have gained traction and will solidify the need to have skilled reproductive endocrinology and infertility surgeons in our practice.

Meeting the challenge of unclaimed cryopreserved embryos.

With the rise of efficient and highly effective embryo cryopreservation techniques, the modern in vitro fertilization laboratory has unintentionally become a long-term storage facility for embryos and gametes. One challenge posed by long-term storage is the issue of unclaimed, effectively abandoned, cryopreserved embryos whose owners cannot be identified or are unable to provide a dispositional decision. Given the nuanced nature of dealing with human tissue, no straightforward solutions for managing this novel scenario have prevailed. In this article, we discuss the problem faced by physicians, clinics, and patients alike when faced with unclaimed cryopreserved embryos. We also review strategies for proactive prevention and resolution of conflicts that may arise when making dispositional decisions.

Antimüllerian hormone is not associated with embryo ploidy in patients with and without infertility undergoing in vitro fertilization with preimplantation genetic testing.

OBJECTIVE: To assess the association between antimüllerian hormone (AMH) and embryo ploidy rates in 2 cohorts of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A): the general population of women pursuing IVF with PGT-A (Infertile cohort) and women pursuing IVF with preimplantation genetic testing for monogenic disorders (PGT-M) owing to the risk of hereditary monogenic diseases (Non-infertile cohort). DESIGN: Retrospective cohort study. SETTING: Academic center. PATIENT(S): Patients undergoing their first cycle of IVF with trophectoderm biopsy and PGT-A or PGT-A and PGT-M in our center between March 2012 and June 2020. Patients of advanced maternal age according to the Bologna criteria (age ≥40 years) and patients who underwent fresh embryo transfers were excluded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proportion of euploid, mosaic, and aneuploid embryos per cycle. RESULT(S): "Infertile" (n = 926) and "Non-infertile" (n = 214) patients were stratified on the basis of AMH levels, with low-AMH defined as <1.1 ng/mL in accordance with the Bologna criteria. Age-adjusted regression models showed no relationship between AMH classification and proportion of euploid, mosaic, and aneuploid embryos in the Infertile or Non-infertile cohorts. In the Infertile cohort, no association between AMH classification and embryo ploidy rates was identified in a subgroup analysis of patients aged <35 years, 35-37 years, and 38-39 years. These findings persisted in a sensitivity analysis of infertile patients stratified into AMH (ng/mL) quartile categories. CONCLUSION(S): No association was found between AMH and the proportion of euploid, mosaic, or aneuploid embryos in 2 large cohorts of patients undergoing IVF with PGT-A (Infertile patients) or PGT-A and PGT-M (Non-infertile patients), suggesting that a quantitative depletion of ovarian reserve does not predict the ploidy status of the embryo cohort.

Pregnancy outcomes after oral and injectable ovulation induction in women with infertility with a low antimüllerian hormone level compared with those with a normal antimüllerian hormone level.

OBJECTIVE: To determine the ongoing pregnancy rate among patients with infertility with a low antimüllerian (AMH) level compared with those with a normal AMH level after oral and injectable ovulation induction (OI)/intrauterine insemination (IUI). DESIGN: Retrospective cohort. SETTING: Academic center. PATIENT(S): Patients completing ≥1 medicated OI/IUI cycle at our center between 2015 and 2019 were included. The AMH levels were measured within 12 months of treatment initiation. The cohort was stratified into low AMH (AMH level, <1.0 ng/mL) and normal AMH (AMH level, ≥1.0 ng/mL) groups. All subsequent medicated OI/IUI cycles occurring within 1 year of initial cycle start date were included up to the third completed cycle or until an ongoing pregnancy was recorded. Patients were stratified by age (<35, 35-40, and >40 years), and the relationship between the low and normal AMH groups and each binary endpoint were quantified as risk ratios using the age-adjusted Poisson models. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ongoing pregnancy. RESULT(S): A total of 3,122 patients completed 5,539 oral antiestrogen cycles, and 1,060 completed 1,630 injectable gonadotropin cycles. For oral antiestrogen treatment, pregnancy outcomes, including ongoing pregnancy rate per cycle, for patients with a low AMH level were comparable with those for patients with a normal AMH level (<35 years, 15.4% vs. 14.9%; 35-40 years, 10.0% vs. 11.0%; and >40 years, 2.8% vs. 3.3%). For injectable gonadotropin treatment, the ongoing pregnancy rate was lower in the low AMH group than in the normal AMH group for the ages of <35 (12.1% vs. 23.5%; relative risk [RR], 0.52 [95% confidence interval {CI}, 0.28-0.97]) and 35-40 (12.5% vs. 18.5%; RR, 0.70 [95% CI, 0.49-0.99]) years but comparable with that for patients aged >40 years (3.0% vs. 4.0%; RR, 0.86 [95% CI, 0.31-2.35]). The proportion of multifetal gestations was similar between the low and normal AMH groups treated with oral antiestrogens (13.1% vs. 10.8%); however, for injectable gonadotropin treatment, patients with a normal AMH level had a higher proportion of multifetal gestations (18.6% vs. 31.1%). CONCLUSION(S): Compared with normal ovarian reserve, treatment with oral antiestrogens for OI/IUI for patients with low ovarian reserve results in comparable follicular development and ongoing pregnancy rates for all age groups. When patients with low ovarian reserve are treated with gonadotropins for OI/IUI, multifollicular recruitment is less likely resulting in a significantly decreased ongoing pregnancy rate for patients aged <35 and 35-40 years but also a decrease in multifetal gestations. Overall, the ongoing pregnancy rates of 8.7% per oral antiestrogen cycle and 8.1% per injectable gonadotropin cycle in patients with low ovarian reserve are comparable with the expected rates in the general infertility population.

Live-Birth Outcomes Among Women With Infertility and Anti-Müllerian Hormone Levels of 0.3 ng/mL or Lower.

OBJECTIVE: To estimate the live-birth rate per in vitro fertilization (IVF) cycle and after cumulative infertility treatment among patients with anti-müllerian hormone (AMH) levels of 0.3 ng/mL or lower. METHODS: We conducted a retrospective cohort study at a single academic center of patients with infertility and AMH levels of 0.3 ng/mL or lower who initiated one or more IVF cycles (2013-2019). Exclusion criteria included prior chemotherapy, hormonal contraceptive use within 3 months of AMH level measurement, and severe male factor infertility. Patients were stratified by Society for Assisted Reproductive Technology (SART) age group. The primary outcome was live-birth rate per IVF cycle. Live-birth outcomes were compared with the 2018 SART National Summary Report for live births per single intended oocyte retrieval, with proportion difference (PD) and 95% CI reported. RESULTS: A total of 978 patients were included. The median (interquartile range) number of cycles initiated was 2 (1-3). With the first initiated cycle, the live-birth rate for those with AMH levels of 0.3 ng/mL or lower was significantly lower in each age category compared with the SART live-birth rate per single initiated cycle (younger than 35 years: 26.2% vs 55.6%, PD 29.4%, 95% CI 20.9-37.9%; 35-37 years: 15.9% vs 40.8%, PD 24.9%, 95% CI 19.0-30.9%; 38-40 years: 12.6% vs 26.8%, PD 14.3%, 95% CI 10.2-18.3%; 41-42 years: 4.7% vs 13.4%, PD 8.7%, 95% CI 5.9-11.6%; older than 42 years: 1.2% vs 4.1%, PD 2.9%, 95% CI 1.5-4.3%). In patients aged 35-37, 38-40, 41-42, and older than 42 years, the cumulative live-birth rate after up to three initiated cycles was comparable with the SART live-birth rate per single initiated cycle but remained significantly lower in patients younger than age 35 years (PD 16.8%, 95% CI 7.3-26.2%). After all treatments were included (cumulative IVF, ovulation induction, and unassisted cycles), live-birth rates were similar to SART live-birth rates per single initiated cycle in all age groups. CONCLUSION: Compared with national outcomes, patients with AMH levels of 0.3 ng/mL or lower had a significantly lower chance of live birth after their first initiated cycle. However, the cumulative live-birth rate after up to three initiated cycles was comparable with national live-birth outcomes per single initiated cycle in patients aged 35 years or older. In patients younger than age 35 years, only when all IVF and non-IVF treatment cycles were included did the cumulative live-birth rate become comparable with the national rate per single IVF cycle.

Advancing paternal age does not negatively impact fresh embryo transfer cycle outcomes.

RESEARCH QUESTION: What is the impact of advancing paternal age, stratifying for maternal age, on fresh embryo transfer cycle outcomes? DESIGN: All first autologous fresh embryo transfer cycles between 2013 and 2019 at a single high-volume academic institution were retrospectively reviewed. Female age was dichotomized along the cohort median of (37 years) (Female-Young [F-Y]: <37 years; Female-Old [F-O]: ≥37 years). Male age was stratified along the cohort median (38 years) and 90th centile (48 years) (Male-Young [M-Y]: <38 years; Male-Intermediate [M-I]: ≤38 and >48 years; Male-Old [M-O]: ≥48 years). The primary outcome of interest was the odds of live birth using logistic regression. Secondary outcomes included odds of implantation, clinical intrauterine pregnancy and pregnancy loss. All models were adjusted for continuous female age, use of surgically retrieved testicular spermatozoa, severe oligozoospermia and cleavage- versus blastocyst-stage embryo transfer. RESULTS: A total of 6704 couples were included and were divided into six groups based on paternal/maternal age groups (F-Y/M-Y: 2288; F-Y/M-I: 750; F-Y/M-O: 97; F-O/M-Y: 679; F-O/M-I: 2310; F-O/M-O: 580). While some associations were seen on univariable logistic regression, none of the groups with increasing paternal age showed any statistically significant differences on multivariable logistic regression with respect to implantation, clinical intrauterine pregnancy, pregnancy loss or live birth. CONCLUSIONS: Advanced paternal age does not impact clinical outcomes in fresh transfer cycles. The authors postulate that IVF with or without intracytoplasmic sperm injection is able to overcome the deleterious effects of advancing paternal age on sperm quality and subsequent embryo performance.

The use of fresh compared to frozen ejaculated sperm has no impact on fresh embryo transfer cycle reproductive outcomes.

PURPOSE: To compare the reproductive outcomes of fresh embryo transfer (ET) cycles utilizing fresh versus frozen ejaculated sperm. METHODS: First autologous fresh embryo transfer cycles at a single high-volume academic institution between 2013 and 2019 were retrospectively reviewed. IVF cycles using ejaculated sperm were included, and cycles using donor or surgically retrieved sperm were excluded. Sperm concentration was stratified as ≥ 5 and < 5 million/ml. The primary outcome was live birth, and the secondary outcomes were clinical intrauterine pregnancy (IUP) and miscarriage. A multivariable logistic regression model for the aforementioned outcomes was adjusted a priori for sperm concentration as well as maternal and paternal age. RESULTS: A total of 6128 couples were included. Of these, 5780 (94.3%) utilized fresh sperm, and 348 (5.7%) frozen sperm. A total of 5716 (93.2%) had sperm concentrations ≥ 5 million/ml and 412 (6.7%) had sperm concentrations < 5 million/ml. On multivariable logistic regression, the use of freshly ejaculated sperm was not associated with significantly different odds of clinical IUP, miscarriage, or live birth when compared to cycles using frozen sperm. CONCLUSION: For couples conceiving via fresh ET, the use of fresh versus frozen ejaculated sperm is not associated with reproductive outcomes.

A framework approach for hysteroscopic uterine septum incision: partial and complete.

OBJECTIVE: To demonstrate safe and efficient techniques for hysteroscopic partial and complete uterine septum incisions with radiofrequency electrosurgery. Review of these techniques may be particularly helpful for a surgical trainee or a less experienced hysteroscopic surgeon. DESIGN: Video instruction of the hysteroscopic uterine septum incision techniques. SETTING: Academic hospital setting. PATIENT(S): One patient with a partial uterine septum and 1 patient with a complete uterine septum and a duplicated cervix (2 distinct external cervices) (1). INTERVENTION(S): Hysteroscopic partial and complete uterine septum incisions with a 7-mm unipolar knife electrode. Importantly, the demonstrated techniques can be performed using any hysteroscopic cutting instrument with which the surgeon is comfortable. MAIN OUTCOME MEASURE(S): Surgical techniques that can be used to safely and efficiently incise a uterine septum and determine when the incision is complete. RESULT(S): For a partial uterine septum, surgical techniques include uterine septum shortening, uterine septum thinning, and measurement of the residual septum length with the operating instrument to determine when the incision is complete. Visualization of the tubal ostia should be used throughout the procedure to maintain a horizontal incision plane. For a complete uterine septum with a duplicated cervix, we additionally demonstrate how to make a window through the septum at the level of the internal os to incise the uterine body portion while preserving the tissue wall inferiorly that separates the duplicated cervices. CONCLUSION(S): Uterine septum incision is typically a short procedure that can be successfully performed with operative hysteroscopy. However, if a systematic approach is not followed, the surgeon can quickly and unknowingly become disoriented, resulting in inadvertent uterine perforation, incomplete septum incision, or excessive septum incision causing myometrial thinning, which has been shown to increase the risk of uterine rupture during pregnancy. In practice, the choice of technique used for septum incision should be made intraoperatively and will depend on the septum size and shape. Often, septum shortening, thinning, and residual measurement are best used in combination to achieve a successful result. Surgeons will find the use of these techniques helpful to maintain intraoperative orientation and provide a framework to guide adequate removal of either a partial or complete uterine septum.