Sleep and obstructive sleep apnea in women with infertility.

PURPOSE: Obstructive sleep apnea (OSA) is associated with polycystic ovarian syndrome (PCOS), a common cause of infertility. Understanding predictors and outcomes of OSA in women with infertility may guide treatment. METHODS: A descriptive cross-sectional survey was performed to assess OSA in women presenting to an infertility clinic using validated sleep questionnaires to assess sleep and fertility outcomes. An Infertile-C group (controls with male or tubal factors) and an Infertile-S group (unknown/other infertile causes) were analyzed to assess OSA risk and other sleep disorders (e.g., restless legs syndrome (RLS) and insomnia) with fertility outcomes (time to pregnancy, PCOS, irregular menstruation, and miscarriage). RESULTS: In 258 women, occurrences of OSA diagnosis (6%) and RLS (10%) were reported similar to women of child-bearing age in the general population. PCOS was unassociated with OSA risk. Predictors of OSA risk were BMI, insomnia symptoms, and sleep aid use. Obese women with high OSA risk were more likely to have other comorbidities (e.g., depression). In adjusted models, prior clinical OSA diagnosis was associated with miscarriage (odds ratio: 6.17 (1.24, 30.62), p = 0.026). RLS was associated with irregular menstruation (odds ratio: 3.73 (1.21, 11.53), p = 0.022). CONCLUSIONS: Similar to other populations, women with infertility and OSA risk have more health comorbidities and higher BMI and may present with insomnia symptoms. While the data are limited, this study supports the potential associations of OSA and miscarriage. Further work is needed to evaluate OSA in female infertility.

Uterine Transplantation: Recipient Patient Populations.

Uterine transplantation is an emerging treatment for patients with uterine factor infertility (UFI). In order to determine patient candidacy for transplant, it is imperative to understand how to identify, counsel and treat uterine transplant recipients. In this article, we focus on patient populations with UFI, whether congenital or acquired, including Mayer-Rokitansky-Kuster-Hauser, complete androgen insensitivity syndrome, hysterectomy, and other causes of nonabsolute UFI. Complete preoperative screening of recipients should be required to assess the candidacy of each individual prior to undergoing this extensive treatment option.

Characterizing the endometrial fluid cytokine profile in women with endometriosis.

PURPOSE: To 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. METHODS: Patients 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. RESULTS: Endometrial 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-1ß, 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%. CONCLUSION: Aspiration 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-1ß, and IL-6 in the endometrial secretions is predictive of stage 3-4 endometriosis, but is not predictive of minimal-to-mild disease.

Effect of surgery on ovarian reserve in women with endometriomas, endometriosis and controls.

BACKGROUND: Many women who experience endometriosis and endometriomas also encounter problems with fertility. OBJECTIVE: The purpose of this study was to determine the impact of surgical excision of endometriosis and endometriomas compared with control subjects on ovarian reserve. STUDY DESIGN: This was a prospective cohort study of 116 women aged 18-43 years with pelvic pain and/or infertility who underwent surgical treatment of suspected endometriosis (n=58) or endometriomas (n=58). Based on surgical findings, the suspected endometriosis group was further separated into those with evidence of peritoneal disease (n=29) and those with no evidence of endometriosis (n=29). Ovarian reserve was measured by anti-Müllerian hormone and compared before surgery and at 1 month and 6 months after surgery. RESULTS: Baseline anti-Müllerian hormone values were significantly lower in the endometrioma vs negative laparoscopy group (1.8 ng/mL [95% confidence interval, 1.2-2.4 ng/mL] vs 3.2 ng/mL [95% confidence interval, 2.0-4.4 ng/mL]; P<.02), but the peritoneal endometriosis group was not significantly different than either of these groups. Only patients with endometriomas had a significant decline in ovarian reserve at 1 month (-48%; 95% confidence interval, -54 to -18%; P<.01; mean anti-Müllerian hormone baseline value, 1.77-1.12 ng/mL at 1 month). Six months after surgery, anti-Müllerian hormone values continued to be depressed from baseline but were no longer significantly different. The rate of anti-Müllerian hormone decline was correlated positively with baseline preoperative anti-Müllerian hormone values and the size of endometrioma that was removed. Those with bilateral endometriomas (n=19) had a significantly greater rate of decline (53.0% [95% confidence interval, 35.4-70.5%] vs 17.5% [95% confidence interval, 3.2-31.8%]; P=.002). CONCLUSION: At baseline, patients with endometriomas had significantly lower anti-Müllerian hormone values compared with women without endometriosis. Surgical excision of endometriomas appears to have temporary detrimental effects on ovarian reserve.

Surgical Innovations to Protect Fertility from Oncologic Pelvic Radiation Therapy: Ovarian Transposition and Uterine Fixation.

As oncologic therapy continues to advance, survivorship care has widened the realm of possibilities for quality-of-life improvements, including fertility preservation and restoration. We aim to summarize the current and future directions of fertility preservation techniques for patients facing gonadotoxic medical therapies who desire pregnancy after their condition is treated. This review of both ovarian and uterine transposition highlights the present roles, techniques, and fertility outcomes of the two fertility preservation treatment modalities designed to protect reproductive organs from harmful pelvic radiation. Current evidence shows that ovarian transposition preserves ovarian function for patients with localized pelvic radiation demonstrating the most successful return of fertility. Uterine transposition holds great promise for patients desiring to conceive and carry a full-term pregnancy after radiation therapy. With ongoing advancements in oncologic treatments leading to increased survival rates, fertility is increasingly becoming a key survivorship issue. Patients can anticipate counseling about these fertility preservation surgical techniques that protect both the ovaries as well as the uterus from harmful pelvic radiation.

Racial disparities in telehealth use during the coronavirus disease 2019 pandemic.

OBJECTIVE: To investigate the impact of coronavirus disease 2019 on initial infertility consultations. DESIGN: Retrospective cohort. SETTING: Fertility practice in an academic medical center. PATIENTS: Patients presenting for initial infertility consultation between January 2019 and June 2021 were randomly selected for prepandemic (n = 500) and pandemic (n = 500) cohorts. EXPOSURE: Coronavirus disease 2019 pandemic. MAIN OUTCOME MEASURES: The primary outcome was a change in the proportion of African American patients using telehealth after pandemic onset compared with all other patients. Secondary outcomes included presentation to an appointment vs. no-show or cancellation. Exploratory outcomes included appointment length and in vitro fertilization initiation. RESULTS: The prepandemic cohort vs. the pandemic cohort had fewer patients with commercial insurance (64.4% vs. 72.80%) and more African American patients (33.0% vs. 27.0%), although the racial makeup did not differ significantly between the two cohorts. Rates of missed appointments did not differ between the cohorts, but the prepandemic cohort vs. the pandemic cohort was more likely to no-show (49.4% vs. 27.8%) and less likely to cancel (50.6% vs. 72.2%). African American patients, compared with all other patients, during the pandemic were less likely to use telehealth (57.0% vs. 66.8%). African American patients, compared with all other patients, were less likely to have commercial insurance (prepandemic: 41.2% vs. 75.8%; pandemic: 57.0% vs. 78.6%), present to their scheduled appointment (prepandemic: 52.7% vs. 73.7%; pandemic: 48.1% vs. 74.8%), and cancel vs. no-show (prepandemic: 30.8% vs. 68.2%, pandemic: 64.3% vs. 78.3%). On multivariable analysis, African American patients were less likely (odds ratio 0.37, 95% confidence interval 0.28-0.50) and telehealth users were more likely (odds ratio 1.54, 95% confidence interval 1.04-2.27) to present to their appointments vs. no-show or cancel when controlling for insurance type and timing relative to the onset of the pandemic. CONCLUSION: Telehealth implementation during the coronavirus disease 2019 pandemic decreased the overall no-show rate, but this shift did not apply to African American patients. This analysis highlights disparities in insurance coverage, telehealth utilization, and presentation for an initial consultation in the African American population during the pandemic.

Uterus Transplantation: Revisiting the Question of Deceased Donors versus Living Donors for Organ Procurement.

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.

TEAM(ing): together each achiev(ing) more!

Providing medical care at the highest levels across various reproductive endocrinology and infertility settings necessitates seamless partnership among multiple people with diverse skill sets. In this introductory article for this month's Views and Reviews, the concept of teaming is presented, including the key concepts of collaboration, assembling the right team members, establishing goals, inspiring and empowering others, and encouraging new approaches to optimize outcomes. Following this introduction, thought leaders from diverse reproductive endocrinology and infertility spaces, including clinical, ambulatory surgery, laboratory, and research settings, present their experiences using teaming models to adapt team members' thinking, elevate the quality of scientific productivity, and achieve excellence in both patient care and laboratory and clinical outcomes.

Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology.

Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti-PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.

Left upper quadrant laparoscopic placement: effects of insertion angle and body mass index on distance to posterior peritoneum by magnetic resonance imaging.

OBJECTIVE: To determine the ideal angle for insertion of laparoscopic instruments at Palmer's point. STUDY DESIGN: Abdominal magnetic resonance images were reviewed for 75 women between ages 18 and 50 years old. The distance from the skin to the retroperitoneal structures were determined perpendicular to the spine and angled 45 degrees caudally. RESULTS: When instruments are inserted perpendicular to the skin in the axial plane and peritoneum perpendicular to the spine, the distance from skin to posterior was 10.0 +/- 0.2 cm and to the aorta was 11.3 +/- 0.2 cm. If instruments are inserted at an angle 45 degrees caudally, this distance increased to 16.6 +/- 0.2 cm. CONCLUSION: When inserting laparoscopic instruments at Palmer's point, insertion perpendicular to the skin in the axial plane and angled 45 degrees caudally in relation to the spine offers an increased margin of safety compared with insertion perpendicular to the spine, particularly in thin women.

Fertility Preservation in Women With Endometriosis.

Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, both because of the pathophysiology of the disease and iatrogenic injury resulting from surgical intervention. Fertility preservation must occur at multiple levels, including careful selection of surgical candidates, avoidance of repeat procedures, and meticulous surgical technique. Fertility preservation with oocyte or ovarian tissue cryopreservation may be considered on an individual basis for women with endometriosis, particularly those at risk of bilateral ovarian injury, such as women with bilateral endometriomas.

Management of Endometriomas.

IMPORTANCE: Endometriomas are a unique and complex representation of the classic phenotypes of endometriosis. Associated symptoms, high recurrence rate, and multimodal approach represent ongoing challenges in the management of this chronic disease. OBJECTIVE: To review current literature regarding medical and surgical management of endometriomas. EVIDENCE ACQUISITION: An extensive literature search including PubMed and Cochrane Library was performed. Review was performed using the following key words: "endometrioma," "cystectomy," "chronic pain," "infertility," "IVF," "menopause," "recurrence." All pertinent articles were assessed. The references of those articles were then reviewed, and additional publications were evaluated. Eligibility of the studies was first assessed on titles and abstracts. Full articles were then reviewed for all selected studies, and decision for final inclusion was made at that time. CONCLUSIONS AND RELEVANCE: Cystectomy of ovarian endometriomas has been the first-line treatment for management for many years because it provides improved pain relief, reduces recurrence rates, and was thought to be favorable in in vitro fertilization. However, a growing body of evidence is demonstrating benefit, or at least no harm, in expectant management for asymptomatic patients with small, stable endometriomas. Medical management is often very effective and appropriate first line. When surgical intervention is appropriate, careful ovarian cyst excision with goal of ovarian tissue preservation and treatment of additional endometriosis by a trained surgeon can provide the patient the best long-term outcome and preservation of ovarian tissue and function.

Fertility preservation in pediatric female cancer patients.

OBJECTIVE: To describe and demonstrate ovarian tissue cryopreservation (OTC) as an emerging fertility preservation technique DESIGN: Video presentation. SETTING: University hospital. PATIENT(S): A 6 year-old female patient diagnosed with aplastic anemia with plan for bone marrow transplantation underwent laparoscopic unilateral oophorectomy in conjunction with surgical procedure for port placement by the pediatric surgeon, followed by cryopreservation of ovarian tissue. INTERVENTION(S): Laparoscopic unilateral oophorectomy followed by ovarian decortication in the operating room, and ovarian tissue freezing prior to undergoing bone marrow transplantation. MAIN OUTCOME MEASURE(S): To present principle surgical techniques of ovarian tissue harvesting prior to OTC in pediatric patients, and different surgical techniques for ovarian auto-transplantation of cryobanked ovarian tissue after completion of gonadotoxic treatment and when the patient is ready to conceive. RESULT(S): This video demonstrates the detailed surgical technique for ovarian tissue harvesting. This harvesting can be performed laparoscopically or via mini-laparotomy and can involve a complete oophorectomy versus removing a portion of the ovary (a procedure also known as ovarian decortication). CONCLUSION(S): In the prepubertal child, due to the small size of the ovaries, we recommend oophorectomy rather than decortication owing to the small size of prepubertal gonadal tissue. Many young cancer patients can be offered the option of ovarian tissue freezing. This tissue contains immature primordial follicles that can be stored. OTC requires surgical ovarian harvesting followed by cryopreservation of strips of ovarian tissue. The increased number of eggs in prepubertal children underscores the fact that smaller ovarian size in this population does not preclude OTC. At this time, ovarian auto-transplantation is the only option to utilize this stored tissue for fertility preservation. OTC is a relatively new procedure within the area of ART. The overall data from OTC is reassuring and further suggests that cryopreservation of ovarian tissue has the potential to become an established fertility preservation method in the near future.

Ovarian transposition: a surgical option for fertility preservation.

OBJECTIVE: To describe and demonstrate a novel surgical method for laparoscopic ovarian transposition. In this video, we present a unique minimally invasive technique for transposing the ovaries, whereby the ovary is tunneled through the peritoneum. DESIGN: Video presentation of clinical article. The video uses animations and a surgical case to demonstrate the detailed surgical technique for laparoscopic ovarian transposition with a unique feature. Institutional review board approval was not required for this video presentation. Institutional review board approval is not required at the Cleveland Clinic for a case report of a single patient. SETTING: Teaching University. PATIENT(S): A 29-year-old female patient diagnosed with rectal cancer. INTERVENTION(S): The patient underwent laparoscopic ovarian transposition followed by ovarian decortication for ovarian tissue freezing of the contralateral ovary, both performed in one laparoscopic surgery, before further chemotherapy and radiation. MAIN OUTCOME MEASURE(S): Value and feasibility of laparoscopic ovarian transposition using the unique feature of ovarian tunneling in maintaining the retroperitoneal location of the ovarian vessels and potentially preserving ovarian blood supply. RESULT(S): Creating a retroperitoneal tunnel for passing the ovary through is a feasible and effective technique, while performing laparoscopic ovarian transposition that can be performed in order to prevent the ovarian vessels from taking a sharp turn into the pelvic cavity and thereby preventing alteration of ovarian blood flow. CONCLUSION(S): Ovarian transposition is a great surgical option for fertility preservation in reproductive-aged women before they undergo gonadotoxic pelvic or craniospinal radiation. This surgical procedure is not a beneficial option for those patients receiving concomitant gonadotoxic chemotherapy. Ovarian transposition can be performed using different surgical techniques, including laparotomy and laparoscopy. Laparoscopic ovarian transposition is the preferred surgical technique described in the literature, because it is associated with more rapid recovery and less postoperative pain. This technique has been reported to have a success rate of 88.6% for preservation of ovarian function, as documented by measuring the gonadotropin levels after cancer treatment. Ovarian transposition is considered to be a safe and effective surgical option to prevent from premature ovarian failure and to optimize preservation of fertility.