Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Predicting personalized cumulative live birth following in vitro fertilization.

OBJECTIVE: To develop in vitro fertilization (IVF) prediction models to estimate the individualized chance of cumulative live birth at two time points: pretreatment (i.e., before starting the first complete cycle of IVF) and posttreatment (i.e., before starting the second complete cycle of IVF in those couples whose first complete cycle was unsuccessful). DESIGN: Population-based cohort study. SETTING: National data from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System. PATIENT(S): Based on 88,614 women who commenced IVF treatment using their own eggs and partner's sperm in SART member clinics. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The pretreatment model estimated the cumulative chance of a live birth over a maximum of three complete cycles of IVF, whereas the posttreatment model did so over the second and third complete cycles. One complete cycle included all fresh and frozen embryo transfers resulting from one episode of ovarian stimulation. We considered the first live birth episode, including singletons and multiple births. RESULT(S): Pretreatment predictors included woman's age (35 years vs. 25 years, adjusted odds ratio 0.69, 95% confidence interval 0.66-0.73) and body mass index (35 kg/m2 vs. 25 kg/m2, adjusted odds ratio 0.75, 95% confidence interval 0.72-0.78). The posttreatment model additionally included the number of eggs from the first complete cycle (15 vs. 9 eggs, adjusted odds ratio 1.10, 95% confidence interval 1.03-1.18). According to the pretreatment model, a nulliparous woman aged 34 years with a body mass index of 23.3 kg/m2, male partner infertility, and an antimüllerian hormone level of 3 ng/mL has a 61.7% chance of having a live birth over her first complete cycle of IVF (and a cumulative chance over three complete cycles of 88.8%). If a live birth is not achieved, according to the posttreatment model, her chance of having a live birth over the second complete cycle 1 year later (age 35 years, number of eggs 7) is 42.9%. The C-statistic for all models was between 0.71 and 0.73. CONCLUSION(S): The focus of previous IVF prediction models based on US data has been cumulative live birth excluding cycles involving frozen embryos. These novel prediction models provide clinically relevant estimates that could help clinicians and couples plan IVF treatment at different points in time.

The Adolescent and Young Adult (AYA) Horizon Study: An AYA Cancer Survivorship Cohort.

BACKGROUND: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States. METHODS: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data. RESULTS: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall (N = 1,679), and notably lower among minority groups compared with non-Hispanic white women. CONCLUSIONS: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements. IMPACT: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.

Ambient Air Pollution Exposure and Fecundability in Women Undergoing In Vitro Fertilization.

BACKGROUND: Limited research suggests ambient air pollution impairs fecundity but groups most susceptible have not been identified. We studied whether long-term ambient air pollution exposure prior to an in vitro fertilization (IVF) cycle was associated with successful livebirth, and whether associations were modified by underlying infertility diagnosis. METHODS: Data on women initiating their 1st autologous IVF cycle in 2012-13 were obtained from four U.S. clinics. Outcomes included pregnancy, pregnancy loss, and livebirth. Annual average exposure to fine particulate matter (PM2.5), PM10, and nitrogen dioxide (NO2) prior to IVF start were estimated at residential address using a validated national spatial model incorporating land-use regression and universal kriging. We also assessed residential distance to major roadway. We calculated risk ratios (RR) using modified Poisson regression and evaluated effect modification (EM) by infertility diagnosis on additive and multiplicative scales. RESULTS: Among 7,463 eligible participants, 36% had a livebirth. There was a non-significant indication of an association between PM2.5 or NO2 and decreased livebirth and increased pregnancy loss. Near roadway residence was associated with decreased livebirth (RR: 0.96, 95% CI: 0.82, 0.99. There was evidence for EM between high exposure to air pollutants and a diagnosis of diminished ovarian reserve (DOR) or male infertility and decreased livebirth. CONCLUSIONS: Despite suggestive but uncertain findings for the overall effect of air pollution on fecundity, we found a suggestive indication that there may be synergistic effects of air pollution and DOR or male infertility diagnosis on livebirth. This suggests two possible targets for future research and intervention.

Risk of prematurity and infant morbidity and mortality by maternal fertility status and plurality.

PURPOSE: To evaluate the risk of prematurity and infant mortality by maternal fertility status, and for in vitro fertilization (IVF) pregnancies, by oocyte source and embryo state combinations. METHODS: Women in 14 States who had IVF-conceived live births during 2004-13 were linked to their infant's birth and death certificates; a 10:1 sample of non-IVF births was selected for comparison; those with an indication of infertility treatment on the birth certificate were categorized as subfertile, all others were categorized as fertile. Risks were modeled separately for the fertile/subfertile/IVF (autologous-fresh only) group and for the IVF group by oocyte source-embryo state combinations, using logistic regression, and reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: The study population included 2,474,195 pregnancies. Placental complications (placenta previa, abruptio placenta, and other excessive bleeding) and prematurity were both increased with pregestational and gestational diabetes and hypertension, among subfertile and IVF groups, and in IVF pregnancies using donor oocytes. Both subfertile and IVF pregnancies were at risk for prematurity and NICU admission; IVF infants were also at risk for small-for-gestation birthweight, and subfertile infants had greater risks for neonatal and infant death. Within the IVF group, pregnancies with donor oocytes and/or thawed embryos were at greater risk of large-for-gestation birthweight, and pregnancies with thawed embryos were at greater risk of neonatal and infant death. CONCLUSIONS: Prematurity was associated with placental complications, diabetes and hypertension, subfertility and IVF groups, and in IVF pregnancies, donor oocytes and/or thawed embryos.

National survey of the Society for Assisted Reproductive Technology membership regarding insurance coverage for assisted reproductive technologies.

OBJECTIVE: To assess the attitudes of Society for Assisted Reproductive Technology (SART) members regarding expanding insurance coverage for patients seeking assisted reproductive technologies (ART) and identify some of the factors that may influence such attitudes. DESIGN: An anonymous online 14-question survey of SART membership; 1,556 surveys were sent through the SART Research Portal from June to December 2017. Questions were incremental in scope, beginning with expanding insurance coverage for ART for vulnerable populations (e.g., fertility preservation for cancer, couples with same recessive gene, fertility preservation for transgender individuals) to extending coverage to include patients who were uninsured for ART. Additional questions assessed attitudes about assuming some fiscal responsibility if mandated insurance were contingent on elective single-embryo transfer (eSET) and lower charges in anticipation of increased number of cases. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Specific response to 14 survey questions. RESULT(S): The overall response rate was 43.4% (675/1,556). A large majority (>95%) favored insurance for fertility preservation for cancer patients and for avoidance of genetic disorders; 62.3% were supportive of infertility insurance coverage for transgender patients; 78% supported expanding insurance for the broadest segment of the general uninsured population; 76.7% supported expanding insurance contingent on eSET; and 51.3% would consider expanding insurance contingent on lowering charge per cycle in general, but only 23% responded as to what lower charge would be acceptable. Three of four factors were shown by multivariable logistic regression to be predictive of attitudes willing to expand insurance: practice setting (academic > hybrid > private), practicing in a mandated state, and higher annual volume of cases (>500 cycles); these had significant increased adjusted odds ratios ranging from 1.7 to 2.9. A fourth factor, the professional role one had in the practice, was not found to be of significant predictive value. CONCLUSION(S): The great majority of respondents were supportive of expanding insurance for specific segments of vulnerable populations with special needs and for the population who are presently uninsured. Furthermore, the majority of respondents would consider expanding insurance coverage contingent on age-appropriate eSET but have concerns about reduced reimbursement. Those most likely to be willing to expand insurance are those who practice in an academic setting or a mandated state and/or have a high annual volume of cases.

Comparisons of matrix metalloproteinase 1, 2, and 9 activity in periovulatory follicular fluid from natural and stimulated menstrual cycles.

We studied the activity levels of matrix metalloproteinase 1, 2, and 9 in periovulatory fluids from naturally occurring menstrual cycles versus those from samples taken from menstrual cycles stimulated with clomiphene citrate or recombinant stimulating hormone. No statistically significant differences were found.

Plasma matrix metalloproteinase activity during the menstrual cycle of healthy ovulatory patients who underwent tubal ligation.

The plasma profiles of active metalloproteinase (MMP)-1, MMP-2, and MMP-9 levels during the normal menstrual cycle in ovulating, healthy and tubal ligated patients were studied. The active MMP-1 and MMP-9 plasma levels were found to vary in the menstrual cycle. Active MMP-2 levels, however, are constant during the menstrual cycle.

Applications of intraoperative ultrasound in gynecological surgery.

PURPOSE OF REVIEW: Gynecologists are well trained in office-based ultrasound, but are less experienced in the field of intraoperative ultrasound. Many gynecologic procedures may benefit from the use of real-time ultrasonography. The purpose of this review is to summarize the current use of intraoperative ultrasound in gynecologic procedures. RECENT FINDINGS: Evaluation and assessment of the value of intraoperative ultrasound in gynecological procedures is essentially non-existent. The role of intraoperative ultrasound in gynecology is in its infancy, with anecdotal experience and literature involving predominantly case reports. Intraoperative ultrasound is helpful in laparoscopic myomectomy, particularly when the uterine contour is normal. It is also useful in defining pelvic anatomy in cases of complex reproductive procedures. Intraoperative ultrasound improves precision in characterizing ovarian lesions, particularly in the setting of endometriomas or dermoid cysts. It has been shown to decrease both operative time and complication rates in dilation and curettage procedures. Intraoperative ultrasound reduces recurrence and re-operation rates after hysteroscopy by facilitating more-complete resection of uterine myomas. Ultrasound guidance improves the efficiency of embryo transfer in in-vitro fertilization and could potentially be beneficial in other 'blind' gynecological procedures. SUMMARY: Intraoperative ultrasound appears to be a safe and valuable tool for the gynecologic surgeon. Ultrasound improves visualization of anatomy, reduces complication and re-operation rates, and facilitates completion of more cases via less-invasive endoscopic approaches.

Intraoperative ultrasound during a laparoscopic myomectomy.

OBJECTIVE: To report a gynecologic use of a laparoscopic ultrasound transducer to isolate a myoma for surgical removal. DESIGN: Case report. SETTING: University-based infertility practice. PATIENT(S): A 44-year-old woman gravida 1 para 1 with history of a first trimester miscarriage who desired pregnancy as a participant in the donor egg program. INTERVENTION(S): Before she entered the assisted reproduction program, a patient was found to have a myoma that was greater than 2 cm with both intramural and submucosal components. During the laparoscopic evaluation, a laparoscopic ultrasound transducer helped identify and properly locate the myoma in what otherwise appeared to be a normal uterus. Appropriate laparoscopic hysterotomy incision was then made, thereby minimizing uterine trauma. MAIN OUTCOME MEASURE(S): Appropriately placed hysterotomy incision and successful reconstruction of uterus. RESULT(S): After the successful laparoscopic myomectomy, the patient achieved a pregnancy in our donor oocyte program. CONCLUSION(S): Laparoscopic intraoperative ultrasound can help gynecologic surgeons complete a laparoscopic myomectomy.

Reproductive outcomes in women with uterine anomalies.

PURPOSE: Because of diagnostic improvements in the evaluation of uterine anomalies, more patients desirous of pregnancy come to clinicians with identified uterine anomalies. It is desirable for the family physician, internist, and obstetrician/gynecologist to provide accurate information during preconceptional counseling of these patients. This review attempts to provide a concise summary of the current English-speaking literature concerning the reproductive outcome in women with uterine anomalies following both natural conceptions and those pregnancies occurring with assisted reproductive techniques (ART). METHODS: A literature review of reproductive anomalies and pregnancy outcomes was performed using PubMed databases. Obstetrical outcomes were compiled from the medical literature and compared with the known rates of pregnancy outcomes in subjects presumed to have normal uterine anatomy. RESULTS: In general, obstetrical complications, such as preterm delivery and first trimester miscarriage, are higher in women with abnormal uteri. Women with an arcuate uterus have a similar reproductive outcome to women with a normal uterus. The unicornuate uterus has the poorest overall reproductive outcome, and the septate uterus has an increased miscarriage rate. The didelphic uterus, historically thought to have no adverse reproductive outcomes, also has poor obstetrical outcomes. Didelphic, bicornuate, unicornuate, and septate uteri have lower pregnancy rates in ART. CONCLUSIONS: Women with uterine anomalies have poorer reproductive outcomes and lower pregnancy rates with all conceptions whether spontaneous or induced with ART compared with women with normal uteri.

Female genital anomalies affecting reproduction.

OBJECTIVE: A multitude of female congenital anomalies are uncommon. However, their impact on reproduction can be profound. The aim of this review is to remind the practicing physician of the clinically relevant embryology and summarize the studies that look at the impact of such various anomalies on a woman's fecundity. We review particular surgical therapies that possibly may improve fertility in such women. DESIGN: Review and critique of available studies in which particular surgical therapies were done and whether they truly improved fertility in these women with congenital reproductive anomalies. RESULTS: Clear evidence demonstrates that uterine septum resection is effective in women with demonstrated recurrent pregnancy losses. Arcuate uterus has little impact on reproduction. Other studies fail to definitively show that surgical correction will improve pregnancy retention or fertility except for specifically indicated clinical scenarios. CONCLUSIONS: The practicing reproductive specialist should have working knowledge of evidence-based therapeutic options for women with reproductive congenital anomalies. A summary chart has been devised to clearly associate embryologic structures with normal adult derivative as well as anomalous structures.