Reproductive Endocrinology Practice Research Articles

Changes to reproductive endocrinology and infertility practice, research, and training as investor mergers increase

Private equity investment in fertility clinics has rapidly increased and is leading to unprecedented changes in the field of reproductive endocrinology and infertility (REI). The goal of this paper was to review private equity's current integration in REI and discuss both benefits and challenges of investor involvement. We found that at least 25% of fellowship programs and medical schools were affiliated with private practice fertility clinics, not free-standing academic clinics. Approximately half of medical schools and nearly all REI fellowship programs that were affiliated with private practices were also backed by private investors. Research participation remains robust in private equity-affiliated REI clinics. With the changing infrastructure, we discuss the potential influence on trainee experience and research while also acknowledging the unique advantages that investor involvement may offer.

Macroprolactin and macroprolactinaemia: A narrative review

Background: Macroprolactin is a heteropolymeric complex of monomeric prolactin and immunoglobulin G (IgG) with little or no biological activity in vivo. Macroprolactinaemia is a notable cause of misdiagnosis and unnecessary treatment of patients with biochemical hyperprolactinaemia. Hence, it needs to be excluded in all patients with laboratory-established increase in serum prolactin levels. The polyethylene-glycol (PEG) precipitation method is commonly used for the routine laboratory screening for macroprolactinaemia. Objective: To review the concept of macroprolactinaemia and its impact on the clinical manifestations, biochemical features, laboratory and radiological evaluations, and management of patients with hyperprolactinaemia. Method: Review of available literature and selected references on macroprolactinaemia and its contribution to the aetiology of biochemical hyperprolactinaemia. Conclusion: Macroprolactinaemia is diagnostically and clinically important in reproductive endocrinology practice. Routine laboratory screening of macroprolactinaemia using the PEG-precipitation method is highly recommended for all cases of hyperprolactinaemia.

Bearing Witness to Joy and Sorrow: Narrative Medicine and Reproductive Endocrinologist and Infertility (REI) Providers’ Journeys in Infertility Treatment

ABSTRACT This study examines providers’ perceptions of provider-patient communication in reproductive endocrinology and infertility (REI) practices. Grounded in narrative medicine, we interviewed six REI providers about their experiences providing fertility care. REI providers crafted a narrative of bearing witness by (1) situating personal and professional self in REI narratives, (2) sharing news as important medical moments, and (3) cultivating affiliation between provider and patient. These findings offer insight into the power of narrative medicine in fertility care, the role of emplotment in narrative sense-making, and the emotional labor associated with information delivery in REI treatments. We offer several recommendations for how patients and providers can improve communication experiences in REI.

Intraovarian condensed platelet cytokines for infertility and menopause—Mirage or miracle?

On a therapeutic landscape unchanged since the 1980's, oocyte donation with IVF still stands as the solitary medical answer to diminished reserve and premature ovarian insufficiency. In 2016, intraovarian platelet-rich plasma (PRP) crossed the horizon as a hopeful reply to these intertwined problems. The once remote mirage of platelet cytokine effects on gene regulation or telomere stabilization has been brought into sharper focus, with current work clarifying how PRP corrects oxidative stress, rectifies tissue hypoxia, downregulates apoptosis, and enhances cellular metabolism. Not yet ready for routine use, this innovative treatment has already offered at least one point of early consensus: How intraovarian PRP results should be classified—Patients are either responders or non-responders. From this it is intriguing that no published PRP protocol has ever reported a supranormal ovarian rebound or hyperstimulation effect. This might be explained by baseline age-related ovarian conditions prevalent among poor responders, but since dysregulated or malignant transformations are also missing in other tissue contexts following autologous PRP treatment, the contribution of some platelet product which intrinsically delimits regenerative action cannot be discounted. Here we summarize results with recent experimental and clinical platelet research, framing those most likely to help advance reproductive endocrinology practice.

On the shoulders of giants: perspectives in minimally invasive reproductive surgery

The purpose of this video is to illustrate the evolution of minimally invasive surgery from the perspectives of several pioneering surgeons in the field of reproductive surgery who, among others, were present during its nascence and exponential growth. Interviews were conducted with five reproductive surgeons who had foundational roles in the innovation of operative laparoscopy and hysteroscopy. Surgeons interviewed include Drs. Victor Gomel, Togas Tulandi, Stephen Corson, Jacques Donnez, and Camran Nezhat. The interviews were conducted using standardized questions and recorded, edited, and grouped both thematically and in sequence to develop an illustration of their perspectives. A diverse array of reproductive surgeons has been instrumental in establishing minimally invasive surgery as a safe and effective means of diagnosing and treating patients with infertility. The transition from laparotomy to laparoscopy consistently has had distinct challenges for each but ultimately led to significant advances in surgical management and improvement in outcomes for patients with infertility and chronic pelvic pain. Through structured interviews from some of our surgical pioneers, they not only recognize their predecessors and contemporaries but also teach us valuable lessons about our history, sparking innovation, and newer surgical applications of reproductive surgery in reproductive endocrinology and infertility practice.

Provision of infertility care for the underserved in reproductive endocrinology and infertility practices associated with obstetrics and gynecology residency training programs in the United States

ObjectiveTo survey practice patterns designed to increase access to infertility care and evaluate the exposure of obstetrics and gynecology residents to infertility care for the underserved.DesignCross-sectional.SettingReproductive endocrinology and infertility (REI) practices associated with Accreditation Council for Graduate Medical Education-accredited obstetrics and gynecology residency training programs.Patient(s)None.Intervention(s)Questionnaire survey.Main Outcome Measure(s)Presence of clinical programs designed to improve access to REI care, resident involvement in such programs, and perceived barriers to expanding access to care.Result(s)Clinical initiatives to expand access included discounted infertility services (38%, n = 30), utilization of a low-cost in vitro fertilization (IVF) program (28%, n = 22), and utilization of a resident- and/or fellow-staffed clinic to provide infertility care (39%, n = 31). The most commonly discounted infertility services were IVF (73%, n = 22), clinical consultation (70%, n = 21), and intrauterine insemination (53%, n = 16). The provision of discounted prices was correlated with the increasing practice size (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.23–4.24) and number of assisted reproductive technology cycles performed annually (OR, 3.65; 95% CI, 1.48–9.02). Academic REI practices (OR, 3.6; 95% CI, 0.98–13.25) were more likely to have a low-cost IVF program. Less than half of obstetrics and gynecology residency programs (39%, n = 31) had an associated REI clinic in which obstetrics and gynecology residents provide direct infertility care to the medically underserved. Frequency and services offered in trainee clinics varied. Multiple barriers to expanding access to care were reported.Conclusion(s)Reproductive endocrinology and infertility practices associated with obstetrics and gynecology residency programs utilize a diverse range of approaches to provide infertility care to the underserved in the backdrop of considerable challenges and barriers, but significant gaps persist.

Outcomes of embryo transfers performed by Reproductive Endocrinology and Infertility fellows vs. faculty: an 11-year retrospective review

To compare the clinical pregnancy rate (CPR) and live birth rate (LBR) of embryo transfer episodes (ETEs) performed by Reproductive Endocrinology and Infertility fellows vs. those of ETEs performed by faculty physicians. Retrospective cohort analysis. Academic reproductive endocrinology and infertility practice. In total, 3,073 ETEs for 1,488 unique patients were performed by fellows or faculty physicians between January 2009 and January2020. None. Clinical pregnancy rate and LBR. Fifteen fellows performed 1,225 (39.9%) of 3,073 ETEs after completing 30 mock transfers. On comparing outcomes among fellowship years (FY1, FY2, and FY3), CPR (44.1% vs. 43.2% vs. 45.7%, respectively, P = .83) and LBR (39.1% vs. 38.1% vs. 38.4%, respectively, P = .97) were not significantly different. Fellowship year 1 fellows' initial 30 ETEs vs. all the remaining FY1 ETEs had a significantly higher CPR (48.1% vs. 40.5%, respectively, P = .030) and LBR (45.4% vs. 34.3%, respectively, P = .001). There were no significant differences between faculty versus fellow ETEs in terms of CPR (43.0% vs. 45.0%, respectively, P = .30) or LBR (37.3% vs. 39.8%, respectively, P = .16), even after adjusting for patient age, body mass index, primary infertility diagnosis, autologous vs. donor oocyte, fresh vs. frozen embryo, number of embryos transferred, type of transfer catheter, and year of transfer (P = .32 for CPR, P = .22 for LBR). Appropriately trained FY1 fellows had success rates maintained throughout all FYs. There were no significant differences in clinical outcomes between fellow- and faculty-performed transfers. These data demonstrated that allowing fellows to perform live embryo transfers is not detrimental to clinical outcomes.

TELEHEALTH PROVIDER EXPERIENCE IN REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY CLINICS DURING THE COVID-19 PANDEMIC AND BEYOND

To assess Telehealth services offered by Society for Assisted Reproductive Technology (SART) member clinics and provider experiences with incorporating Telehealth into reproductive endocrinology and infertility practices.

Early experience with universal SARS-CoV-2 testing in a New York-based reproductive endocrinology ‎practice

ABSTRACT The SARS-CoV-2 pandemic peak around March 2020 led to temporary closures of most fertility clinics. Many clinics reopened but required universal SARS-CoV-2 screening. However, the rate of positive results and the necessity for such testing is unknown. We report here on early results from asingle-center academic NewYork fertility practice utilizing universal SARS-CoV-2 screening. This mixed prospective retrospective cohort included 164 patients who underwent at least one SARS-CoV-2 screening test for fertility treatment between May and July2020. Patients completed 1 to 3 nasopharyngeal SARS-CoV-2 tests per cycle and remained symptom-free to continue fertility treatments. SARS-CoV-2 test results, past results, history of Covid-19 infection, and patient/cycle characteristics were recorded and tabulated through October2020. Outcomes included positive SARS-CoV-2 RNA tests, rate of prior Covid-19 infections, and clinical courses of patients testing positive. Patients underwent 263 cycles entailing 460 total SARS-CoV-2 screening tests. Fifteen patients reported astrong prior clinical history of Covid-19. Six patients experienced apositive SARS-CoV-2 test (2.3% of all cycles). Among 77 cycles (n = 58 patients) entailing one SARS-CoV-2 test, 2 cases (2.6%) were noted. Among 173 cycles (n = 121 patients) entailing two SARS-CoV-2 tests, 4 cycles (2.3%) were noted. Zero (0%) of 13 cycles (n = 13 patients) entailing 3 SARS-CoV-2 tests were positive. All patients were cleared to resume treatment within one month. Overall, anew asymptomatic infection was identified in 2 cycles (0.8%), while 4 of the 6 positive SARS-CoV-2 tests were among patients with aprior history of Covid-19. 3 of 4 also had adocumented prior positive RNA test. Our data suggest that universal SARS-CoV-2 screening among fertility patients is feasible, with an approximately 2% positive rate per cycle among the patients of this study. Most positive patients had aprior remote infection, but their infectiousness while being screened remains unclear. Abbreviations: REI: reproductive endocrinology and infertility; IUI: intrauterine insemination; IVF: in vitro fertilization; sono: sonography; cryo: cryopreservation; FET: frozen embryo transfer.

Expanded carrier screening for recessively inherited disorders: economic burden and factors in decision-making when one individual in a couple is identified as a carrier.

When undergoing expanded carrier screening (ECS), couples are often screened sequentially to reduce need for a second individual's test. It is unknown how often partners of individuals found to be carriers complete the recommended testing with a sequential approach and what factors contribute to decision-making regarding partner testing. Additionally, the economic burden placed on individuals by ECS testing and its effect on partner testing has not been evaluated. In part 1, all individuals at a university-affiliated reproductive endocrinology and infertility practice identified to be carriers of a recessively inherited mutation using the Counsyl/Foresight ECS were included. Conditions were categorized by severity according to a previously described classification system. In part 2, all individuals who underwent ECS with a single test provider between September 1, 2013 and February 1, 2020 were contacted via email to complete a confidential and anonymized online survey. In part 1, a total of 2061 patients were screened. 36.9% were carriers of one or more recessively inherited disorders. Twenty-seven percent of positively screened individuals did not have their partner screened. Carriers of a moderate condition had a trend towards a reduced odds for having their partner screened compared to a profound condition (OR 0.36, 95% CI 0.12-1.05, p = 0.06). Number of conditions was not predictive of subsequent partner screening (OR 0.95, 95% CI 0.72-1.25, p = 0.72). In part 2, the cost of ECS was not covered by insurance for 54.5% (103/189) and most paid over $300 out-of-pocket for testing (47.6%). The most common reason for not completing partner testing was that the results would not alter their course when seeking conception (33.3%). 73.5% of patients knew that the largest benefit of ECS comes from knowing a partner's results as well as their own. Not all carriers of recessively inherited disorders choose to undergo partner screening. Patients found to be carrier of more debilitating genetic disorders may be more likely to screen their reproductive partners. For many, ECS testing is not covered by insurance, and this test may impose a significant economic burden. For some patients, the results of ECS would not change what they would do when seeking conception. Providers should evaluate whether a patient's ECS result would change their treatment course prior to testing.

Risk factors for atypical hyperplasia and endometrial cancer in the infertility population: a case-control study

Objective To estimate the incidence and identify risk factors for atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in American women undergoing infertility evaluation. Design Case-control study. Setting Academic reproductive endocrinology and infertility practice. Patient(s) Female patients (18–50 years) seeking infertility evaluation from January 1, 2009 to December 1, 2018. Patients with known genetic predisposition to cancer or prior cancer diagnosis were excluded. Cases were defined as patients diagnosed with AH or EC during infertility workup (n = 22). Controls without AH or EC were randomly selected in a 10:1 ratio (n = 220) from all women undergoing infertility evaluation in the same year. Intervention(s) None. Main Outcome Measure(s) Incidence of AH or EC and odds of AH or EC accounting for age, race, body mass index (BMI), and ovulatory dysfunction. Result(s) Twenty-two cases of AH or EC were identified among 11,569 women undergoing infertility evaluation (incidence 2 per 1,000 women, 95% confidence interval [CI] 1.2–2.9 per 1,000). Of these women, 68% had a BMI ≥30 kg/m2 compared with 25% of controls. In multivariable analyses, women with a BMI ≥30 kg/m2 were 5.9 times more likely to be diagnosed with AH or EC (adjusted odds ratio 5.9, 95% CI 2.0–17.2). Women with ovulatory dysfunction were 3.4 times more likely to be diagnosed with AH or EC (adjusted odds ratio 3.4, 95% CI 1.1–10.1). Conclusion(s) The incidence of AH and EC in a population of women undergoing infertility evaluation is 10 times that in the general population of premenopausal women. Obesity is the strongest independent risk factor for AH and EC in women with infertility.

Telenursing and Nurse-Patient Communication Within Fertility, Inc.

The purpose of this study is to examine patient perceptions of practitioner-patient communication in reproductive endocrinology and infertility (REI) practices. During this study, we uncovered the importance of telenursing for nurse-patient communication during REI treatment. Telenursing, which is defined as the use of wireless technology for out-of-office communication, is the basis for out-of-office communication. We examined participants' conceptualization of supportive and unsupportive communication, through the lens of biomedicalization theory. After conducting 23 interviews, we conclude that telenursing is integral to providing holistic nursing care during treatment at REI practices. We discuss efficient and effective uses of telenursing and patients' positive perceptions telenursing and assess telenursing as both an embrace of and form of resistance to biomedicalization within Fertility, Inc. Theoretical and practical implications are offered, including suggestions for increasing patient access to telenursing while protecting REI nurses from burnout.

Fertility preservation during cancer treatment: The Korean Society for Fertility Preservation clinical guidelines.

While many fertility preservation (FP) options now exist for reproductive-aged cancer patients, access to these services continues to be limited. A comprehensive FP program should be organized to serve oncofertility patients effectively. Also, much effort is needed from various individuals—patients, specialists from various fields, and consultants—to facilitate FP in a timely manner. Various challenges still exist in improving access to FP programs. To improve access to FP treatment, it is important to educate oncologists and patients via electronic tools and to actively navigate patients through the system. Reproductive endocrinology practices that receive oncofertility referrals must be equipped to provide a full range of options on short notice. A multidisciplinary team approach is required, involving physicians, nurses, mental health professionals, office staff, and laboratory personnel. The bottom line of FP patient care is to understand the true nature of each patient's specific situation and to develop a patient flow system that will help build a successful FP program. Expanding the patient flow system to all comprehensive cancer centers will ensure that all patients are provided with adequate information regarding their fertility, regardless of geography.

Effects of fertility drugs on cancers other than breast and gynecologic malignancies

To examine the relationship of ovulation-stimulating drugs to risk of cancers other than breast and gynecologic malignancies. Retrospective cohort study, with additional follow-up since initial report. Reproductive endocrinology practices. Among a cohort of 12,193 women evaluated for infertility between 1965 and 1988, a total of 9,892 women (81.1% of the eligible population) were followed through 2010, via passive and active (questionnaire) approaches. None. Hazard ratios (HRs) and 95% confidence intervals (CIs) for various fertility treatment parameters for select cancers. During 30.0 median years of follow-up (285,332 person-years), 91 colorectal cancers, 84 lung cancers, 55 thyroid cancers, and 70 melanomas were diagnosed among study subjects. Clomiphene citrate (CC), used by 38.1% of patients, was not associated with colorectal or lung cancer risks, but was related significantly to melanoma (HR = 1.95; 95% CI: 1.18-3.22), and non-significantly to thyroid cancer risks (HR = 1.57; 95% CI: 0.89-2.75). The highest melanoma risks were seen among those with the lowest drug exposure levels, but thyroid cancer risk was greatest among the heavily exposed patients (HR = 1.96; 95% CI: 0.92-4.17 for those receiving >2,250 mg). Clomiphene citrate-associated risks for thyroid cancer were somewhat higher among nulligravid, compared with gravid, women, but did not differ according to distinct causes of infertility. Gonadotropins, used by only 9.7% of subjects, were not related to risk of any of the assessed cancers. Our results provide support for continued monitoring of both melanoma and thyroid cancer risk among patients receiving fertility drugs.

Spanish language content on reproductive endocrinology and infertility practice websites

To analyze the use of Spanish language translation on the websites of reproductive endocrinology and infertility (REI) practices in the context of evidence of underuse of infertility services by minority populations. Cross-sectional survey of websites from REI practices. Not applicable. None. None. Assessment of the relationship between having a Spanish-translated website and REI practice characteristics. Variables included concurrent use of social media, size of the practice, Spanish-speaking practitioner in the practice, being a private or a university-based practice, being in a mandated insurance state, and being in an area with different levels of percentage of Hispanic population, adjusted for annual income levels of the population. Of the 376 REI practice websites analyzed, 101 (27%) offered at least some information in Spanish. We identified 97 Spanish-speaking practitioners at 71 REI practices. Having a Spanish-translated website was significantly associated with the practice's use of social media, having an international/out-of-town web page, and having a Spanish-speaking physician in the practice. The size of the practice, as measured in number of cycles reported per year, was not associated with having a translated website. In practices located in the top 60 metropolitan areas by Hispanic population, the odds of having a Spanish-translated website were only related to the percentage of Hispanic population after adjusting for state-mandated insurance and average annual income level of the Hispanic population. Sixty-six of the websites with Spanish-translated content had been automatically translated. An additional eight websites were partially translated automatically. REI practices in metropolitan areas with a higher percentage of Hispanics were more likely to reach out to this minority population by translating their website content into Spanish. These practices were also more likely to use social media. Future studies are needed to determine whether the availability of Spanish language content on REI websites is associated with increased use of reproductive services by this minority population.

Se habla espanol? how reproductive endocrinology practices reach out to spanish speaking patients in the united states

To analyze the use of Spanish language translation on the websites of Reproductive Endocrinology and Infertility (REI) practices in the context of the projected growth of Hispanics as health consumers and evidence of underutilization of infertility services by minority populations.

An assessment of current clinical attitudes toward letrozole use in reproductive endocrinology practices

To assess the clinical use and practice attitudes among Society for Assisted Reproductive Technology (SART) members regarding the use of letrozole for ovulation induction and infertility treatment. The SART clinic physicians were mailed a cover letter and consent form, a two-page survey, and return envelope. The surveys were returned and analyzed using descriptive statistics. Not applicable. None. A 13-question survey. Reproductive endocrinology and infertility physicians use patterns and attitudes regarding letrozole. A total of 77.9% of physician prescribe letrozole. Of those who do not, 32.4% cited concern about the US Food and Drug Administration warning, 35.1% cited satisfaction with current medications, 25.7% cited both reasons, and 6.8% cited no experience with letrozole. Physicians (11.5%) were unaware of the US Food and Drug Administration warning. Physicians (99.7%) were aware that ovulation induction is an off-label use of letrozole. The most common use was for ovulation induction in patients with polycystic ovary syndrome (PCOS). Physicians (14.9%) prescribe letrozole as first-line ovulation therapy prior to clomid, 47.9% use for clomid failures, and 25.7% reported use in both situations. Most physicians surveyed use letrozole for ovulation induction despite the current US Food and Drug Administration warning. Even when accounting for nonrespondents, more than 25% of physicians indicated success with letrozole use. Questions regarding doses and clinical concerns about letrozole revealed no standardized manner of letrozole administration despite wide interest, therefore additional research is warranted.

Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles.

Ovulation-inducing drugs and ovarian cancer risk: results from an extended follow-up of a large United States infertility cohort

To examine the relationship of ovulation-inducing drugs and ovarian cancer. Retrospective cohort study, with additional follow-up since initial report. Five large reproductive endocrinology practices. In a retrospective cohort of 9,825 women evaluated for infertility at five clinical sites in the United States between 1965 and 1988 with follow-up through 2010, we examined the relationship of ovulation-inducing drugs and ovarian cancer (n = 85). None. Hazard rate ratios (RR) and 95% confidence intervals (CI) for ovarian cancer. Among women evaluated for infertility, there was no association of ovarian cancer risk with ever use of clomiphene citrate (CC) (adjusted RR 1.34, 95% CI 0.86-2.07) or gonadotropins (RR 1.00, 95% CI 0.48-2.08) and no evidence that any of several more detailed subgroups of usage were related to an increased risk with one exception: women who used CC and remained nulligravid did demonstrate much higher risks than those who successfully conceived compared with nonusers (respectively, RR 3.63, 95% CI 1.36-9.72 vs. RR 0.88, 95% CI 0.47-1.63). Our overall results were reassuring and consistent with other studies. A reason for an association between CC use and ovarian cancer among persistently nulligravid women remains to be determined. Given the large and increasing number of women treated with ovulation-inducing drugs, the increased risk of ovarian cancer among the subset of women who remained nulligravid should be further monitored.

Embryology training for reproductive endocrinology (RE) fellows in the clinical human embryology laboratory: comprehensive training on actual clinical cases with excellent patient outcomes

IVF has become the cornerstone of clinical RE practice and is a major focus of contemporary research. In spite of the critical nature of the IVF process, most REs receive minimal training and do not typically participate in clinical embryology care. This is in contrast to other laboratory procedures where fellows are expected to gain technical proficiency with any procedure that they utilize clinically or in research. This fellowship program requires fellows to spend 6 months in the clinical embryology lab learning and performing each aspect of human embryology from basic dish prep to complex micromanipulation.