Ovulation induction with letrozole and dexamethasone in infertile patients with letrozole-resistant polycystic ovary syndrome.

PURPOSE: To assess efficacy of adjuvant dexamethasone during letrozole cycles for ovulation induction (OI) in women with letrozole-resistant polycystic ovary syndrome (PCOS). METHODS: We retrospectively evaluated 42 cycles of OI from 28 infertile women with letrozole-resistant PCOS between September 2019 and November 2022. Letrozole was initiated on cycle day 3 for 5 days and increased via a stair-step approach to 7.5 mg as indicated. Patients were deemed letrozole-resistant if no dominant follicle was identified on transvaginal ultrasound following this dose. Resistant patients then received 5 additional days of letrozole 7.5 mg with low-dose dexamethasone 0.5 mg for 7 days and had a repeat ultrasound. The primary outcome was ovulation rate determined by the presence of a dominant follicle on ultrasound. Secondary outcomes included endometrial thickness, number of measurable follicles, and pregnancy outcomes among responders. RESULTS: Twenty-two of 28 (79%) letrozole-resistant PCOS patients had evidence of ovulation after the addition of dexamethasone in 35 out of 42 (83%) cycles. Clinical pregnancy occurred in 20% of ovulatory cycles with a cumulative rate of 32%. All clinical pregnancies resulted in a live birth. Patients who responded to adjuvant dexamethasone were more likely to have a shorter duration of infertility; however, there were no differences in other demographics, serum androgens including DHEA-S, or pretreatment glycemic status. CONCLUSION: Adding dexamethasone to letrozole increased ovulation rates in letrozole-resistant PCOS patients undergoing OI with similar pregnancy outcomes to prior studies. The addition of dexamethasone is an effective, inexpensive, and safe option for PCOS patients otherwise at risk for cycle cancelation.

Thyroid hormone levels associate with exposure to polychlorinated biphenyls and polybrominated biphenyls in adults exposed as children.

BACKGROUND: Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure's effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB. METHODS: Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T4), total triiodothyronine (T3), free T4, free T3, thyroid stimulating hormone (TSH), and free T3: free T4 ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry. RESULTS: Higher PBB levels were associated with many thyroid hormones measures, including higher free T3 (p = 0.002), lower free T4 (p = 0.01), and higher free T3: free T4 ratio (p = 0.0001). Higher PCB levels were associated with higher free T4 (p = 0.0002), and higher free T3: free T4 ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 (N = 446), higher PBB exposure was associated with higher total T3 (p = 0.01) and free T3 (p = 0.0003), lower free T4 (p = 0.04), and higher free T3: free T4 ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted. CONCLUSIONS: This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally.

National mosaic embryo transfer practices: a survey.

BACKGROUND: The growing use of preimplantation genetic testing with in vitro fertilization has provided clinicians with more information about the genetics of embryos. Embryos, however, sometimes result with a mixed composition of both aneuploid and euploid cells, called mosaic embryos. The interpretation of these results has varied, leading some clinicians to transfer mosaic embryos and some opt not to. In addition, laboratories providing preimplantation genetic testing for aneuploidy have differing thresholds for determining an embryo aneuploid, mosaic, or euploid. Overall practice patterns for mosaic embryo transfer practices in the United States are unknown. OBJECTIVE(S): The objectives of the study were to characterize national mosaic embryo transfer practices, including the use of preimplantation genetic testing for aneuploidy, prior history of transferring mosaic embryos, thresholds for determining mosaicism, and willingness to transfer mosaic embryos among assisted reproductive technology clinics in the United States. STUDY DESIGN: A 14 question online survey assessing current use of preimplantation genetic testing for aneuploidy, thresholds for determining mosaicism, and clinic experience and willingness to transfer mosaic embryos was e-mailed to 405 assisted reproductive technology clinics across the United States. Descriptive statistics and logistic regression were used to analyze survey responses and identify clinical factors associated with reporting having ever transferred a mosaic embryo. RESULTS: Of the 405 US assisted reproductive technology clinics contacted, 252 (62.2%) completed a survey, including 157 private (62.3%), 55 academic (21.8%), and 40 hybrid (15.9%) clinics. Most clinics (168, 66.7%) reported conducting preimplantation genetic testing for aneuploidy on less than 50% of all in vitro fertilization cycles. The most common type of preimplantation genetic testing for aneuploidy technology used was next-generation sequencing at 88.9%. Ninety-one clinics (36.1%) receive mosaicism data on their preimplantation genetic testing for aneuploidy report; the most common thresholds for determining embryo aneuploidy and euploidy by clinics' primary genetics laboratories were <20% normal (36.3%) and >80% normal (46.2%), respectively. Thirty-nine (42.9%) of the 91 have transferred and 57 (62.6%) would transfer a mosaic embryo. Nearly 40% of clinics were unsure about their thresholds for mosaic transfer and one fourth of clinics reported they had no threshold. Private (odds ratio, 1.0, 95% confidence interval, 0.5-1.8) and hybrid (odds ratio, 0.9, 95% confidence interval, 0.4-2.1) clinics were just as likely as academic clinics to report having transferred a mosaic embryo. Clinics in the northeastern United States were more likely to have transferred a mosaic embryo than clinics in other regions (odds ratio, 1.5, 95% confidence interval, 0.9-2.7). Most clinics (72.6%) report they do not have a unique consent for transfer of mosaic embryos. CONCLUSION: There is uncertainty and variability in the transfer practices of mosaic embryos and classification of mosaicism among US assisted reproductive technology clinics. These findings provide an opportunity to establish mosaicism thresholds and create standardized guidelines for transferring mosaic embryos.

Surgical Management of Endometriosis Involving the Bladder and Ureter.

BACKGROUND: Endometriosis is a chronic, debilitating condition affecting up to 10% of reproductive-age women. Urinary tract endometriosis is found in 1%-6% of women diagnosed with pelvic endometriosis, with the most common sites being the bladder (70%-85%), ureter (9%-23%), and kidney (4%). Patients typically present with symptoms such as lower abdominal pain, dysuria, and urgency. Unfortunately, urinary tract endometriosis is often asymptomatic, potentially leading to silent obstructive uropathy and kidney failure. OBJECTIVE: To demonstrate a step-by-step approach for the surgical management of urinary tract endometriosis using conventional laparoscopy for partial cystectomy and robotic-assisted laparoscopy for ureteroneocystostomy. MATERIAL AND METHOD: Surgical video of 2 cases managed in an academic tertiary referral center for endometriosis. The first case was a 38-year-old Gravida 3, Para 3 with a history of hysterectomy who had an MRI which revealed a T2 hypointense bladder nodule consistent with endometriosis. Patient had significant urinary urgency, dysuria, and suprapubpic pain that improved but did not disappear after starting oral progestin therapy (5 mg of norethindrone). A cystoscopy was first performed to confirm MRI findings of bladder lesion and to delineate borders and depth of invasion. The second case was a 35-year-old nulliparous woman with chronic pelvic pain and primary infertility. The patient had a history of stage IV endometriosis with deep endometriosis into the bowel and extrinsic encasement of the ureters causing subsequent hydronephrosis requiring bilateral ureteral stents. She had continued daily pelvic pain despite of being on oral contraceptives for medical management of endometriosis. She subsequently underwent bilateral percutaneous nephrostomy tube placement to allow for ureteral rest prior to surgery. RESULTS: In the first case, conventional laparoscopy was utilized to perform bilateral ureterolysis, bladder mobilization, partial cystectomy for complete excision of the lesion, and 2-layered bladder closure. Use of indigo carmine assisted with ureteral orifice identification. In the second case, a cystoscopy was performed with injection of Indocyanine green to assist with ureteral identification. After ureterolysis, distal ureteric obstruction due to extensive disease was confirmed on laparoscopy and ureteroscopy. Bilateral ureteroneocystostomy with placement of Double-J ureteral stents was performed using a robotic-assisted approach. Each patient had an indwelling Foley catheter for bladder decompression during recovery. Pathology in both cases revealed endometriosis. Both patients had an uneventful postoperative course. A postoperative retrograde cystogram confirmed adequate repair prior to removal of each Foley catheter. Patient 2 had uncomplicated office stent removal 6 weeks postoperatively and had a normal renal ultrasound with no hydronephrosis 6 months postoperatively. CONCLUSION: Endometriosis is an increasingly common condition. It is important for gynecological surgeons to have the proper understanding of anatomy, surgical technique, and multidisciplinary care needed with urology for safe and complete excision of bladder and ureter endometriosis.

Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Uterine Leiomyomas.

Uterine leiomyomas are common hormone-responsive neoplasms that frequently cause heavy menstrual bleeding, anemia, pelvic pressure, pain, and adverse reproductive outcomes. In this overview, the efficacy and safety of oral gonadotropin-releasing hormone (GnRH) antagonists, co-administered with menopausal replacement-level steroid hormones or used at doses to avoid complete hypothalamic suppression, are reviewed for the management of uterine leiomyomas. Oral GnRH antagonists provide rapid suppression of sex steroids and avoid the initial steroidal flare and resultant temporary worsening of symptoms typically seen with parenteral GnRH agonists. Oral GnRH antagonists are effective in reducing leiomyoma-associated heavy menstrual bleeding, with high rates of amenorrhea and improved anemia and leiomyoma-associated pain, and providing modest reduction in uterine volume when used in combination with menopausal replacement-level steroid hormones. This add-back therapy can reduce hypogonadal side effects, including hot flushes and bone mineral density loss, close to levels seen with placebo therapy. Currently, both elagolix 300 mg twice daily with once-daily estradiol (1 mg) and norethindrone (0.5 mg) and relugolix 40 mg once daily with estradiol (1 mg) and norethindrone (0.5 mg) combination therapy are approved for leiomyoma treatment by the U.S. Food and Drug Administration. Linzagolix is under investigation in the United States but approved at two does with and without steroid hormones in the European Union. The efficacy of these agents appears to be robust over a wide spectrum of clinical presentations, demonstrating that worse disease parameters at baseline do not appear to inhibit efficacy. Across clinical trials, participants largely reflected the population of individuals affected by uterine leiomyomas.

A step-by-step approach to a frozen pelvis.

OBJECTIVE: To demonstrate a step-by-step approach for restoration of pelvic anatomy in frozen pelvis using a systematic approach to make the steps reproducible, safe, and time efficient. DESIGN: Video presentation. SETTING: Academic medical center. PATIENT(S): A 30-year-old nulliparous woman with lifelong dysmenorrhea and 4 years of infertility who presented for the surgical management of stage IV endometriosis. INTERVENTION(S): An abdominopelvic survey was first in a systematic fashion to assess the extent of adhesive disease and evalaute for normal anatomy. Dissection was then started on the patient's left side to mobilize the sigmoid colon at the pelvic brim. Subsequently, the ureters were identified and bilateral ureterolysis was performed as the retroperitoneal spaces were explored. Once the ureters were safely dissected, the adnexa were mobilized bilaterally. Attention was then turned to the dissection of the medial pararectal spaces (Okabayashi's space) before the dissection of the rectovaginal space. With the restoration of anatomy, the remaining planned surgery was completed. MAIN OUTCOMES MEASURE(S): Restoration of pelvic anatomy, excision of endometriosis, and resolution of symptoms. RESULT(S): The patient had an uncomplicated procedure with complete excision of endometriosis and an estimated blood loss of 45 mL. She was discharged on the same day and had an uneventful postoperative period. At her follow-up appointment, she had resolution of symptoms and was initiated on medical hormone suppression therapy until ready for in vitro fertilization. CONCLUSION(S): A frozen pelvis is a condition in which the pelvic organs are distorted and tethered to each other as a result of adhesive processes. This can obscure normal anatomical landmarks and surgical planes making dissection extremely difficult, thus increasing the risk of interoperative and postoperative complications. Although an uncommon surgical condition, it is not rare to come across in clinical practices, thus creating a challenge to reproductive surgeons as it is commonly seen with endometriosis-associated infertility. It is important for surgeons to be able to recognize the relevant anatomy and have the knowledge to open proper pelvic avascular spaces in the pelvis to mitigate these risks. Following this video's step-by-step approach can help restore pelvic anatomy for planned surgical procedures.

Octopamine and serotonin have opposite effects on antipredator behavior in the orb-weaving spider, Larinioides cornutus.

In this study, we experimentally elevated levels of octopamine and serotonin in an orb-weaving spider, and observed the effects on the antipredator behavior thanatosis (death feigning), activity level, and running speed. We found that octopamine significantly shortened the duration of thanatosis, and its effect wore off over 24 h. We also found that serotonin significantly lengthened thanatosis, but in this case, the effect persisted for over 24 h. Neither octopamine nor serotonin affected the general activity or running speed of the spiders. To our knowledge, this is the first study to directly explore the role of biogenic amines on a specific antipredator behavior in spiders. Given that spiders must be both aggressive toward prey, yet wary of predators, we believe that this system will be an outstanding model to explore connections between behavioral ecology and neurochemistry.

Is there still a role for a cleavage-stage embryo transfer?

OBJECTIVE: To determine whether pregnancy outcomes are poor or futile when an intended day 5 transfer is converted to a cleavage-stage transfer because of poor embryo development or a lower number of embryos. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Women with a limited number of embryos, defined as ≤6 two pronuclear embryos, after in vitro fertilization. INTERVENTIONS: Patients who had a cleavage-stage transfer were age matched with patients who had a day 5 transfer. MAIN OUTCOME MEASURES: Live birth rate. RESULTS: A total of 146 women were included in the study with 73 women in each group. Cleavage-stage transfer was associated with significantly lower implantation and clinical pregnancy rates compared with those of day 5 transfer. Although the live birth rate of the cleavage-stage transfer group was lower than that of the day 5 transfer group (25% vs. 40%, respectively), the cleavage-stage transfer still resulted in a live birth rate of 25%. A subanalysis comparing women who did and did not achieve live birth after cleavage-stage transfer demonstrated a live birth rate of 27% when at least one grade A embryo was transferred vs. 17% when a lesser quality embryo (grade B or C) was transferred. CONCLUSIONS: As expected, the live birth rate after cleavage-stage transfer was lower than that after day 5 transfer. However, the live birth rate of cleavage-stage transfer still fell into acceptable practice, >5%, for patients who were otherwise at very high risk of having no day 5 embryo transfer. Extended culture may not be necessary for all patients.

Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl.

In 1973, accidental contamination of Michigan livestock with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies (â€Šß = -0.11, 95% CI = -0.21 to -0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.

Fertility Considerations in Transgender Persons.

Hormonal therapy and gender-affirming surgeries in transgender people have known deleterious impacts on future fertility using one's own gametes. This review focuses on fertility preservation, including the effects of medical hormone treatment on fertility, available and experimental options of fertility preservation in transgender adults, including sperm cryopreservation for transwomen and oocyte cryopreservation for transmen, and options for prepubertal transgender adolescents, including testicular and ovarian tissue cryopreservation. Transgender patients continue to face barriers and receive infrequent counseling regarding fertility preservation. Physicians should ideally counsel and discuss fertility preservation options before transgender patients undergo hormone therapy of gender-affirmation surgery.