The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women.

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist.

The effect of donor and recipient race on outcomes of assisted reproduction.

BACKGROUND: A growing literature suggests that minority races, particularly Black women, have a lower probability of live birth and higher risk of perinatal complications after autologous assisted reproductive technology. However, questions still remain as to whether these racial disparities have arisen because of associations between race and oocyte/embryo quality, the uterine environment, or a combination of the two. Oocyte donation assisted reproductive technology represents a unique approach to examine this question. OBJECTIVE: This study aimed to evaluate the associations between the race of female oocyte donors and recipients and live birth rates following vitrified donor oocyte assisted reproductive technologies. STUDY DESIGN: This was a retrospective study conducted at a single, private fertility clinic that included 327 oocyte donors and 899 recipients who underwent 1601 embryo transfer cycles (2008-2015). Self-reported race of the donor and recipient were abstracted from medical records. Live birth was defined as the delivery of at least 1 live-born neonate. We used multivariable cluster weighted generalized estimating equations with binomial distribution and log link function to estimate the adjusted risk ratios of live birth, adjusting for donor age and body mass index, recipient age and body mass index, tubal and uterine factor infertility, and year of oocyte retrieval. RESULTS: The racial profile of our donors and recipients were similar: 73% white, 13% Black, 4% Hispanic, 8% Asian, and 2% other. Women who received oocytes from Hispanic donors had a significantly higher probability of live birth (adjusted risk ratio, 1.20; 95% confidence interval, 1.05-1.36) than women who received oocytes from white donors. Among Hispanic recipients, however, there was no significant difference in probability of live birth compared with white recipients (adjusted risk ratio, 1.07; 95% confidence interval, 0.90-1.26). Embryo transfer cycles using oocytes from Black donors (adjusted risk ratio, 0.86; 95% confidence interval, 0.72-1.03) and Black recipients (adjusted risk ratio, 0.84; 95% confidence interval, 0.71-0.99) had a lower probability of live birth than white donors and white recipients, respectively. There were no significant differences in the probability of live birth among Hispanic, Asian, and other race recipients compared with white recipients. CONCLUSION: Black female recipients had a lower probability of live birth following assisted reproductive technology, even when using vitrified oocytes from healthy donors. Female recipients who used vitrified oocytes from Hispanic donors had a higher probability of live birth regardless of their own race.

When using donor oocytes, does embryo stage matter? An analysis of blastocyst versus cleavage stage embryo transfers using a cryopreserved donor oocyte bank.

PURPOSE: Oocyte donor in vitro fertilization (IVF) represents an ideal model to study the effects of embryo stage on reproductive success, as embryos come from young women with high-quality oocytes. Our study aimed to determine if embryo transfer stage affected outcomes in oocyte donor IVF, including the common scenario where only a limited number of quality embryos are available after culture. METHODS: This retrospective cohort analyzed anonymous vitrified donor oocyte cycles at a single clinic between 2008 and 2015. Overall, 983 recipients underwent 1178 warming cycles resulting in fresh transfer of one-to-two embryos. Our primary outcome was live birth; secondary outcomes included multiple birth, birthweight, and gestational age. Log binomial regression with cluster-weighted generalized estimating equations were used to calculate adjusted risk ratios (aRR) accounting for recipient age, race, and transfer year. RESULTS: Among 132 cleavage and 1046 blastocyst transfer cycles, cleavage transfers were associated with lower probability of live birth (aRR 0.72, 95% CI 0.59-0.88). Subgroup analysis focused on cycles with a limited number of quality embryos 3 days post-fertilization (≤2), as clinically these women were most likely to be considered for cleavage transfers. Among these cycles (120 cleavage, 371 blastocyst), cleavage transfers were still associated with lower live birth rates compared to blastocyst (aRR 0.66, 95% CI 0.51-0.87) CONCLUSIONS: Even in a donor oocyte model with high-quality oocytes, there was a benefit to extended culture and blastocyst transfer, including when only one-to-two quality embryos were available after early culture. This is possibly owed to improved uterine synchronicity or decreased contractility.

Endometriosis, endocrine disrupters, and epigenetics: an investigation into the complex interplay in women with polybrominated biphenyl exposure and endometriosis.

PURPOSE: Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to polybrominated biphenyl (PBB). METHODS: Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the ß value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS: In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. CONCLUSION: We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).

Polybrominated Biphenyl Exposure and Menstrual Cycle Function.

BACKGROUND: Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973-1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function. METHODS: In 2004-2006, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine samples for up to 6 months. We assayed the urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35-42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973-1974 (n = 70). RESULTS: We observed that high (>3.0 parts per billion [ppb]) and medium (>1.0-3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure. CONCLUSION: Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.

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.

"Research on Infertility: Definition Makes a Difference" Revisited.

In a 1989 paper, Marchbanks et al. (Am J Epidemiol. 1989;130(2):259-267) noted inconsistent definitions of infertility across research and clinical practice and examined differences in prevalence estimates across definitions. Since their study, there have been substantial changes in society, technology, and clinical practice related to female reproductive health. In response, we revisited the original paper using data from a recent study among reproductive-aged women. Internal comparisons across various definitions of infertility were made by assessing how many and which women were classified as infertile, their age at infertility, and the probability of spontaneous pregnancy after infertility. Results were also compared with Marchbanks et al. Black women were more likely to be classified as infertile than white women based on the definition "12 months of unprotected intercourse" (40.1% vs. 33.7%) but less likely by "12 months of attempting pregnancy" (14.3% vs. 21.8%) and "visiting a doctor for help getting pregnant" (8.4% vs. 19.7%). After unprotected intercourse for 12 months, 36.1% of women who were attempting pregnancy spontaneously conceived by 6 months compared with 13.5% of women who were not attempting pregnancy. While our results for most infertility definitions were similar to those of Marchbanks et al., prevalence estimates continued to differ across demographic groups by definition.

Pregnancy after cancer: Does timing of conception affect infant health?

BACKGROUND: The objective of this retrospective cohort study was to determine whether women who conceive soon after treatment for cancer have higher risks of adverse pregnancy outcomes. METHODS: Vital records data were linked to cancer registry diagnosis and treatment information in 3 US states. Women who conceived their first pregnancy after diagnosis between ages 20 and 45 years with any invasive cancer or ductal carcinoma in situ were eligible. Log-binomial models were used to compare risks in cancer survivors who conceived in each interval to the risks in matched comparison births to women without cancer. RESULTS: Women who conceived ≤1 year after starting chemotherapy for any cancer had higher risks of preterm birth than comparison women (chemotherapy alone: relative risk [RR], 1.9; 95% confidence interval [CI], 1.3-2.7; chemotherapy with radiation: RR, 2.4; 95% CI, 1.6-3.6); women who conceived ≥1 year after starting chemotherapy without radiation or ≥2 years after chemotherapy with radiation did not. In analyses imputing the treatment end date for breast cancer survivors, those who conceived ≥1 year after finishing chemotherapy with or without radiation had no higher risks than women without cancer. The risk of preterm birth in cervical cancer survivors largely persisted but was somewhat lower in pregnancies conceived after the first year (for pregnancies conceived ≤1 year after diagnosis: RR, 3.5; 95% CI, 2.2-5.4; for pregnancies conceived >1 year after diagnosis: RR, 2.4; 95% CI, 1.6-3.5). CONCLUSIONS: In women who received chemotherapy, the higher risk of preterm birth was limited to those survivors who had short intervals between treatment and conception.Cancer 2018;124:000-000.

Fertility preservation options in transgender people: A review.

Gender affirming procedures adversely affect the reproductive potential of transgender people. Thus, fertility preservation options should be discussed with all transpeople before medical and surgical transition. In transwomen, semen cryopreservation is typically straightforward and widely available at fertility centers. The optimal number of vials frozen depends on their reproductive goals and treatment options, therefore a consultation with a fertility specialist is optimal. Experimental techniques including spermatogonium stem cells (SSC) and testicular tissue preservation are technologies currently under development in prepubertal individuals but are not yet clinically available. In transmen, embryo and/or oocyte cryopreservation is currently the best option for fertility preservation. Embryo cryopreservation requires fertilization of the transman's oocytes with a donor or partner's sperm prior to cryopreservation, but this limits his future options for fertilizing the eggs with another partner or donor. Oocyte cryopreservation offers transmen the opportunity to preserve their fertility without committing to a male partner or sperm donor at the time of cryopreservation. Both techniques however require at least a two-week treatment course, egg retrieval under sedation and considerable cost. Ovarian tissue cryopreservation is a promising experimental method that may be performed at the same time as gender affirming surgery but is offered in only a limited amount of centers worldwide. In select places, this method may be considered for prepubertal children, adolescents, and adults when ovarian stimulation is not possible. Novel methods such as in-vitro activation of primordial follicles, in vitro maturation of immature oocytes and artificial gametes are under development and may hold promise for the future.

Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women.

BACKGROUND: Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. METHODS: Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). RESULTS: Total thyroxine (T4 ) concentrations were positively associated with Pd3G and E1 3G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 µg/mg Cr for women with high T4 vs Pd3G = 9.5 and 8.1 µg/mg Cr for women with medium and low T4 , respectively) and greater follicular phase maximum E1 3G (E1 3G = 41.7 ng/mg Cr for women with high T4 vs E1 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T4 , respectively). CONCLUSIONS: Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.

The risk of preterm birth and growth restriction in pregnancy after cancer.

It is unclear whether cancer and its treatments increase the risk of adverse pregnancy outcomes. Our aim was to examine whether cancer survivors have higher risks of poor outcomes in pregnancies conceived after diagnosis than women without cancer, and whether these risks differ by cancer type and race. Diagnoses from cancer registries were linked to pregnancy outcomes from birth certificates in three U.S. states. Analyses were limited to the first, live singleton birth conceived after diagnosis. Births to women without a previous cancer diagnosis in the registry were matched to cancer survivors on age at delivery, parity, race/ethnicity and education. Log-binomial regression was used to estimate risk ratios. Cervical cancer survivors had higher risks of preterm birth (Risk ratio = 2.8, 95% Confidence interval: 2.1, 3.7), as did survivors of invasive breast cancer (RR = 1.3, 95% CI: 1.1, 1.7) and leukemia (RR = 2.1, 95% CI: 1.3, 3.5). We observed a higher risk of small for gestational age (SGA) infants (<10% of weight for age based on a national distribution) in survivors of brain cancer (RR = 1.7, 95% CI: 1.1, 2.8) and extranodal non-Hodgkin lymphoma (RR = 2.3, 95% CI: 1.5, 3.6). We did not see an increased risk of infants born preterm, low birth weight, or SGA in pregnancies conceived after ductal carcinoma in situ, thyroid cancer, melanoma, or Hodgkin lymphoma. While our results are reassuring for survivors of many cancers, some will need closer monitoring during pregnancy.

International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up.

Classical galactosemia (CG) is an inborn error of galactose metabolism. Evidence-based guidelines for the treatment and follow-up of CG are currently lacking, and treatment and follow-up have been demonstrated to vary worldwide. To provide patients around the world the same state-of-the-art in care, members of The Galactosemia Network (GalNet) developed an evidence-based and internationally applicable guideline for the diagnosis, treatment, and follow-up of CG. The guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. A systematic review of the literature was performed, after key questions were formulated during an initial GalNet meeting. The first author and one of the working group experts conducted data-extraction. All experts were involved in data-extraction. Quality of the body of evidence was evaluated and recommendations were formulated. Whenever possible recommendations were evidence-based, if not they were based on expert opinion. Consensus was reached by multiple conference calls, consensus rounds via e-mail and a final consensus meeting. Recommendations addressing diagnosis, dietary treatment, biochemical monitoring, and follow-up of clinical complications were formulated. For all recommendations but one, full consensus was reached. A 93 % consensus was reached on the recommendation addressing age at start of bone density screening. During the development of this guideline, gaps of knowledge were identified in most fields of interest, foremost in the fields of treatment and follow-up.

The effects of hydroxyurea and bone marrow transplant on Anti-Müllerian hormone (AMH) levels in females with sickle cell anemia.

Gonadal hypofunction is described in male and female patients with sickle cell anemia (SCA) after bone marrow transplant (BMT) and in males treated with hydroxyurea (HU). Anti-Müllerian hormone (AMH) is a serum marker of ovarian reserve. This study describes AMH and follicle-stimulating hormone (FSH) levels in female SCA subjects treated with supportive care (SCA-SC), HU (SCA-HU) and BMT (SCA-BMT). SCA (SS/Sß(0)) subjects not on HU, on HU and status-post BMT, ages 10-21 years were recruited. SCA-HU subjects were treated with HU ≥ 20 mg/kg for ≥ 12 consecutive months. SCA-BMT subjects had received busulfan and cyclophosphamide. Serum AMH and random FSH levels were obtained. Diminished ovarian reserve (DOR) was defined as AMH level <5th percentile for age-matched controls. Subjects also with FSH >40 IU/L were classified as having premature ovarian insufficiency (POI). 14 SCA-SC (14.5 ± 2.7 years), 33 SCA-HU (14.4 ± 2.4 years) and 9 SCA-BMT (14.3 ± 2.7 years) females were included. AMH was undetectable in all SCA-BMT subjects and <5th percentile in 24% of SCA-HU subjects. FSH was menopausal (>40 IU/L) in 88.9% of SCA-BMT subjects. All SCA-BMT subjects and 24% of subjects on HU had DOR; 89% of SCA-BMT subjects had POI. AMH and FSH may be useful tools in assessing ovarian reserve and function.

Racial Disparities in Seeking Care for Help Getting Pregnant.

BACKGROUND: Fertility counselling and treatment can help women achieve their desired family size; however, disparities exist in the utilisation of this care. METHODS: This study examines the persistence of a racial disparity in visiting a doctor for help getting pregnant by estimating the direct effect of this association using data from the Furthering Understanding of Cancer Health and Survivorship in Adult Women's Study, a population-based cohort study. This cohort included 1073 reproductive age women (22-45 years) with 28% reporting infertility. We fit log binomial models to quantify the magnitude of the racial difference in reported care seeking after adjustment for hypothesised mediators using inverse probability weighting. RESULTS: Compared with white women, black women were less likely to visit a doctor in the total population [adjusted risk ratio (RR) 0.57, 95% confidence interval (CI) 0.41, 0.80] and in the subgroup of women with infertility [RR 0.75, 95% CI 0.56, 0.99]. In addition, black women waited twice as long, on average, before seeking help compared with white women. CONCLUSIONS: There were notable racial differences in visiting a doctor for help getting pregnant in this study although reports of infertility were similar by race. These differences may be mitigated through improved communication about the range of counselling and treatment options available.

DNA methylation as a window into female reproductive aging.

People with ovaries experience reproductive aging as their reproductive function and system declines. This has significant implications for both fertility and long-term health, with people experiencing an increased risk of cardiometabolic disorders after menopause. Reproductive aging can be assessed through markers of ovarian reserve, response to fertility treatment or molecular biomarkers, including DNA methylation. Changes in DNA methylation with age associate with poorer reproductive outcomes, and epigenome-wide studies can provide insight into genes and pathways involved. DNA methylation-based epigenetic clocks can quantify biological age in reproductive tissues and systemically. This review provides an overview of hallmarks and theories of aging in the context of the reproductive system, and then focuses on studies of DNA methylation in reproductive tissues.

People with ovaries experience a natural decline in the function of their reproductive system as they age. This decline eventually leads to menopause, and after menopause, people have an increased risk of developing cardiovascular or other chronic diseases. In the clinic, it is hard to measure aging of the reproductive system, so other markers of the ovary's function, like the number of remaining eggs, are used. We can also measure reproductive aging using molecular biomarkers, which can help us determine when a person's molecular age is different from their chronological age. This review focuses on an overview of biological processes and theories associated with aging, and then focuses on what can be learned from molecular biomarkers.

The use of fertility treatments among reproductive-aged women after cancer.

OBJECTIVE: To examine whether female cancer survivors are more likely to pursue care for infertility after cancer than women without cancer. DESIGN: Population-based cohort study involving detailed interviews regarding reproductive history. SETTING: Not applicable. PATIENTS: Female cancer survivors aged 22-45 years, who were at least 2 years after a cancer diagnosis between the ages of 20 and 35 years (n = 1,036), and age-matched comparison women with no cancer history (n = 1,026). EXPOSURE: History of cancer vs. no history of cancer. MAIN OUTCOME MEASURE(S): Each cancer survivor was randomly matched to a comparison woman, who was assigned an artificial age at cancer diagnosis equal to that of her match. Matching was repeated 1,000 times. Outcomes of visiting a doctor for help becoming pregnant or undergoing fertility treatment were modeled using Cox proportional hazards regression, comparing survivors after a cancer diagnosis to age-matched comparison women, adjusted for race, income, residence, education, and parity. RESULTS: Only 25.5% of cancer survivors reported meeting their desired family size before a cancer diagnosis. The median time from diagnosis to interview among survivors was 7 (interquartile range 5-11) years. Cancer survivors were more likely to report having no children (32.6%) at the interview compared with women with no cancer history (19.5%). Survivors were not more likely to visit a doctor for help becoming pregnant compared with women without a cancer history, matched on birth year and followed by the age at which cancer survivors received their diagnosis (hazard ratio [HR] 1.16, 95% simulation interval [SI] 0.78-1.74). Compared with cancer-free women, cancer survivors had similar probabilities of pursuing any treatment (adjusted HR [aHR] 0.88, 95% SI 0.46-1.56), using hormones or medications (aHR 0.86, 95% SI 0.46-1.63), or undergoing intrauterine insemination (aHR 1.26, 95% SI 0.40-5.88) to conceive. Cancer survivors were slightly more likely to pursue surgical interventions to become pregnant (HR 1.55, 95% SI 0.67-3.71). Of those who visited a doctor but declined to pursue fertility treatment, one-quarter of women reported declining treatment due to cost. CONCLUSION: Cancer survivors did not use fertility treatments at higher rates than the general population. Further counseling and education surrounding fertility options are recommended for young adult female cancer patients after treatment is completed.

In-utero exposure to polybrominated biphenyl (PBB) and menstrual cycle function in adulthood.

BACKGROUND: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood. METHODS: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). RESULTS: Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) µg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E13G or FSH levels by category of in-utero PBB exposure. CONCLUSION: Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation.

Reproductive health assessment and reports of fertility counseling in pediatric and adolescent patients with sickle cell disease after hematopoietic cell transplantation.

BACKGROUND: Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. OBJECTIVE: The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. STUDY DESIGN: This was a secondary analysis of gonadal hormone production, future infertility risk assessment and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (IQR) or percentages. RESULTS: There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 - 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3,388mg/m2 to 9,706mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥ 40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent-proxies (for patients < 18 years old) and patients ≥ 18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty five percent of parent-proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. CONCLUSION: There are high rates of gonadal dysfunction post-HCT, but many parent-proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

Racial and ethnic disparities in assisted reproductive technology: a systematic review.

There is emergent scientific literature examining the disparities in reproductive care of women in the United States. Reproduction is a basic human right and there are unique challenges that racial and ethnic minorities face in accessing fertility care and assisted reproductive technology. The identification of these disparities can aid in identifying areas for interventions to improve and resolve, the inequities that exist in providing care for minority populations. A literature search was performed using PubMed to identify articles with data specific to racial and ethnic differences in study populations as it related to infertility, access to care, and treatment outcomes. The following review and collection of articles provide a comprehensive overview of the disparities that exist, the factors that contribute to these disparities, and recommendations for how providers and health care systems may begin to resolve the gaps in equitable care.

The Risk of Infertility After Surgery for Benign Ovarian Cysts.

Background: There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Methods: Women aged 22-45 years (n = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Results: Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Conclusions: Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.