Publications by authors named "Jessica B Spencer"

38 Publications

Ovarian stimulation for fertility preservation in women with cancer: A systematic review and meta-analysis comparing random and conventional starts.

J Gynecol Obstet Hum Reprod 2021 Feb 2;50(8):102080. Epub 2021 Feb 2.

Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.

Objective: In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing cancer treatments. Our objective was to compare clinical outcomes among female cancer patients who underwent a conventional early follicular phase-start ovarian stimulation cycle and those who underwent a random-start ovarian stimulation cycle.

Evidence Review: A systematic review of the literature was performed in accordance with PRISMA guidelines. Medline, Embase.com, Scopus, Cochrane Library, and Clinicaltrials.gov databases were searched to identify all original research published in English through July 2020 on the topic of female cancer patients undergoing ovarian stimulation with a random or conventional start. Studies lacking a comparison group or including women who had already undergone chemotherapy at the time of ovarian stimulation were excluded. The primary author assessed all identified article titles and abstracts, and two independent reviewers assessed full-text articles and extracted data. A meta-analysis with a random-effects model was used to calculate weighted mean differences (WMDs) for outcomes of interest. The primary outcome was the number of mature (meiosis II) oocytes retrieved. Secondary outcomes included duration of stimulation, total dose of gonadotropins, total number of oocytes retrieved, fertilization rate, and number of embryos or zygotes cryopreserved.

Results: A total of 446 articles were screened, and 9 full-text articles (all retrospective cohort or prospective observational) were included for review. Additionally, pooled primary retrospective data from two institutions were included. In total, data from 10 studies including 1653 women were reviewed. Five studies reported the number of embryos cryopreserved, and four reported fertilization rates. Random-start cycles were slightly longer (WMD 0.57 days, 95 % confidence interval [CI] 0.0-1.14 days) and used more total gonadotropins (WMD 248.8 international units, 95 % CI 57.24-440.40) than conventional-start cycles. However, there were no differences in number of mature oocytes retrieved (WMD 0.41 oocytes, 95 % CI -0.84-1.66), number of total oocytes retrieved (WMD 0.90 oocytes, 95 % CI -0.21-2.02), fertilization rates (WMD -0.12, 95 % CI -1.22-0.98), or number of embryos cryopreserved (WMD 0.12 embryos, 95 %CI -0.98-1.22) between random-start and conventional-start cycles. All outcomes except for the parameter "total oocytes retrieved" yielded an I of over 50 %, indicating substantial heterogeneity between studies.

Conclusion(s): Although random-start cycles may entail a longer duration of stimulation and use more total gonadotropins than conventional-start cycles, the absolute differences are small and likely do not significantly affect treatment costs. The similar numbers of mature oocytes retrieved, fertilization rates, and number of embryos cryopreserved in the two start-types suggest that they do not differ in any clinically important ways. Given that random-start cycles can be initiated quickly, they may help facilitate fertility preservation for cancer patients.
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http://dx.doi.org/10.1016/j.jogoh.2021.102080DOI Listing
February 2021

Anti-Müllerian hormone in African-American women with systemic lupus erythematosus.

Lupus Sci Med 2020 11;7(1)

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Objective: Women with SLE may experience ovarian insufficiency or dysfunction due to treatment or disease effects. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, has been examined in small populations of women with SLE with conflicting results. To date, these studies have included very few African-American women, the racial/ethnic group at greatest risk of SLE.

Methods: We enrolled African-American women aged 22-40 years diagnosed with SLE after age 17 from the Atlanta Metropolitan area. Women without SLE from the same area were recruited from a marketing list for comparison. AMH was measured in serum using the Ansh Labs assay (Webster, Texas, USA). We considered AMH levels <1.0 ng/mL and AMH <25th percentile of comparison women as separate dichotomous outcomes. Log-binomial regression models estimating prevalence ratios were adjusted for age, body mass index and hormonal contraception use in the previous year.

Results: Our sample included 83 comparison women without SLE, 68 women with SLE and no history of cyclophosphamide (SLE/CYC-) and 11 women with SLE and a history of cyclophosphamide treatment (SLE/CYC+). SLE/CYC+ women had a greater prevalence of AMH <1.0 ng/mL compared with women without SLE (prevalence ratio (PR): 2.90, 95% CI: 1.29 to 6.51). SLE/CYC- women were also slightly more likely to have AMH <1.0 ng/mL (PR: 1.62, 95% CI: 0.93 to 2.82) than comparison women. Results were similar when considering AMH <25th percentile by age of comparison women.

Conclusions: Treatment with CYC is associated with low AMH in African-American women with SLE. SLE itself may also be associated with reduced AMH, but to a lesser extent.
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http://dx.doi.org/10.1136/lupus-2020-000439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607611PMC
November 2020

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

Am J Obstet Gynecol 2020 Sep 12. Epub 2020 Sep 12.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ajog.2020.09.013DOI Listing
September 2020

Hormonal Profiles of Menstrual Bleeding Patterns During the Luteal-Follicular Transition.

J Clin Endocrinol Metab 2020 05;105(5)

Emory University, Rollins School of Public Health, Department of Epidemiology, Atlanta, Georgia.

Context: Menstrual cycle function is determined by a complex endocrine axis that controls the ovaries and endometrium. While the late luteal phase is characterized by declining progesterone and estrogen, how these hormonal profiles relate to menstrual bleeding patterns is not well understood.

Objective: Characterize associations between luteal phase hormonal profiles and subsequent menstrual bleeding patterns, specifically spotting before bleeding.

Design, Setting, And Participants: We examined creatinine-adjusted urinary estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) levels in relation to spotting in 116 premenopausal women (ages 20-47) who kept daily menstrual diaries and collected first morning urine samples for ≥ 2 consecutive cycles or 1 luteal-follicular transition (n = 283 transitions). We used linear mixed models to estimate associations between luteal phase hormone levels and spotting before bleeding.

Main Outcome Measure(s) And Results: Transitions with ≥ 1 days of spotting before menstrual bleeding (n = 118) had greater luteal phase Pd3G levels vs nonspotting transitions (n = 165). Differences in Pd3G between spotting and nonspotting transitions were largest at menses onset (34.8%, 95% confidence interval, 18.9%, 52.7%). Pd3G levels for spotting transitions dropped to similar levels as nonspotting transitions an average of 1 day later, which aligned with the first day of bleeding for transitions with contiguous spotting. Spotting transitions were preceded by slower rates of Pd3G decline than nonspotting transitions, whereas E13G declines were similar.

Conclusions: Self-reported bleeding patterns may provide insight into luteal phase Pd3G levels. First bleed appears to be the best choice for defining the end of the luteal phase and achieving hormonal consistency across transitions.
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http://dx.doi.org/10.1210/clinem/dgaa099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096314PMC
May 2020

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

Sci Rep 2020 02 24;10(1):3314. Epub 2020 Feb 24.

Department of Gynecology and Obstetrics, Emory University School of Medicine, 101 Woodruff Circle NE, Ste 4217, Atlanta, GA, 30322, Georgia.

In 1973, accidental contamination of Michigan livestock with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies ( β = -0.11, 95% CI = -0.21 to -0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.
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http://dx.doi.org/10.1038/s41598-020-60234-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039953PMC
February 2020

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

J Assist Reprod Genet 2020 Feb 5;37(2):427-436. Epub 2020 Feb 5.

Department of Gynecology and Obstetrics, Emory University, 101 Woodruff Circle NE, Suite 4217, Atlanta, GA, 30322, USA.

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 β 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).
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http://dx.doi.org/10.1007/s10815-020-01695-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056781PMC
February 2020

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

Environ Health 2019 08 23;18(1):75. Epub 2019 Aug 23.

Emory University Rollins School of Public Health, 1518 Clifton Rd, Atlanta, GA, 30322, USA.

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 (T), total triiodothyronine (T), free T, free T, thyroid stimulating hormone (TSH), and free T: free T 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 T (p = 0.002), lower free T (p = 0.01), and higher free T: free T ratio (p = 0.0001). Higher PCB levels were associated with higher free T (p = 0.0002), and higher free T: free T 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 T (p = 0.01) and free T (p = 0.0003), lower free T (p = 0.04), and higher free T: free T 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.
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http://dx.doi.org/10.1186/s12940-019-0509-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708149PMC
August 2019

Infertility Among African American Women With Systemic Lupus Erythematosus Compared to Healthy Women: A Pilot Study.

Arthritis Care Res (Hoboken) 2020 09;72(9):1275-1281

Rollins School of Public Health, Emory University, Atlanta, Georgia.

Objective: Some treatments for systemic lupus erythematosus (SLE) can cause infertility, but the effect of SLE itself on fertility, particularly in African American women, is less clear. We undertook this study to examine infertility experiences in African American women with SLE compared to healthy women.

Methods: We enrolled women ages 22-40 years living in the Atlanta metropolitan area who were diagnosed with SLE after age 17 years. Women who had ever been treated with cyclophosphamide or who had a hysterectomy were excluded. African American women ages 22-40 years who were from the same area and recruited from a marketing list were used for comparison. Women were interviewed about their reproductive histories and goals. Periods of infertility were identified as times when women had regular, unprotected sex for ≥12 months without conceiving after 20 years of age. We separately considered any period of infertility and periods of infertility when attempting pregnancy. We used Cox proportional hazards regression to examine the association between SLE and time to infertility. Models were adjusted for age, nulliparity, and smoking. An age-matched analysis was also conducted to examine periods of infertility occurring after SLE diagnosis.

Results: Our sample included 75 women with SLE and 154 women without SLE. SLE was associated with any infertility (adjusted hazard ratio [HR ] 2.08 [95% confidence interval (95% CI) 1.38-3.15]), but less so with infertility when attempting pregnancy (HR 1.30 [95% CI 0.62-2.71]). The matched analysis generated similar point estimates.

Conclusion: Women with SLE may be more likely to experience episodes of infertility, but this may not translate to an inability to meet reproductive goals.
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http://dx.doi.org/10.1002/acr.24022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946885PMC
September 2020

Polybrominated Biphenyl Exposure and Menstrual Cycle Function.

Epidemiology 2019 09;30(5):687-694

From the Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.

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.
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http://dx.doi.org/10.1097/EDE.0000000000001045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679744PMC
September 2019

Effects of Supraphysiologic Levels of Estradiol on Endometrial Decidualization, sFlt1, and HOXA10 Expression.

Reprod Sci 2019 12 4;26(12):1626-1632. Epub 2019 Mar 4.

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.

Objective: Supraphysiologic estradiol (E) levels associated with controlled ovarian hyperstimulation in high in vitro fertilization (IVF) responders may alter implantation and placentation and increase the risk of preeclampsia. Our hypothesis is that elevated E levels in vitro significantly alter endometrial decidualization, sFlt1, and HOXA10 expression.

Methods: Human endometrial stromal cells were treated with a decidualization cocktail of medroxyprogesterone, cyclic adenosine monophosphate, and 3 concentrations of E 10 nM (standard), 100 nM (intermediate), or 1000 nM E (high). Effects on sFlt1, prolactin (PRL), insulin-like growth factor binding protein 1 (IGFBP-1), vascular endothelial growth factor (VEGF), and HOXA10 were studied.

Results: Prolactin, IGFBP-1, and VEGF significantly increased at all 3 E concentrations. While IGFBP-1 and VEGF did not change with increasing E, PRL was less with high E (6.0 ng/mL ± 1.4 standard error of the mean) compared to standard (21.4 ± 3.2) and intermediate (19.8 ± 3.8). sFlt1 decrease was similar at all E concentrations. HOXA10 was lower at standard (10%) and intermediate (30%) as expected, but did not change with high E.

Conclusions: Supraphysiologic E levels associated with high IVF responders that exceed in vivo levels may impair in vitro endometrial decidualization. Although PRL did increase with high E, the levels were, however, attenuated and 3.4-fold lower than standard and intermediate E. sFlt1 was decreased under all 3 conditions with no differences between concentrations. Reduced HOXA10 was not observed with high E. These findings suggest that elevated E levels in vitro may alter endometrial decidualization and subsequently affect implantation and placentation.
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http://dx.doi.org/10.1177/1933719119833485DOI Listing
December 2019

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

Cancer 2018 11 7;124(22):4401-4407. Epub 2018 Nov 7.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1002/cncr.31732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886368PMC
November 2018

Impact of male partner characteristics and semen parameters on in vitro fertilization and obstetric outcomes in a frozen oocyte donor model.

Fertil Steril 2018 10;110(5):859-869

Division of Reproductive Endocrinology & Infertility, Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia.

Objective: To examine the degree to which paternal variables of age, body mass index (BMI), and sperm parameters affect vitrified donor oocyte IVF outcomes. Previous studies examining the impact of male partner characteristics on in-vitro fertilization (IVF) have found conflicting results. Concerns are rising over the potential effects of paternal factors, such as age and obesity, on pregnancy and child health. Frozen donor oocyte IVF offers an ideal model to study these effects.

Design: Retrospective chart review.

Setting: Private fertility clinic.

Patient(s): Nine hundred forty-nine recipients undergoing transfer of blastocyst embryo(s) from a vitrified oocyte donor bank between 2008-2015.

Intervention(s): None.

Main Outcome Measure(s): Implantation rate, clinical pregnancy rate, live birth rate, rate of low birth weight singleton infants (≤2500 g), and preterm deliveries (PTD) of singleton infants (<37 wk).

Results: After adjusting for covariates known to affect oocyte donation cycle success, male age, BMI and sperm parameters were not associated with differences in IVF outcomes. There were higher PTD rates for men ≥51 years and BMI ≥35 kg/m, however, these were not significant after adjustment. There were no differences in rates of low birth weight infants with men >35 years or BMI >25 kg/m. Lastly, there were no differences in rates of PTD or low birth weight infants with abnormal sperm parameters.

Conclusions: Neither advancing male age, elevated BMI, nor poor sperm quality were associated with outcomes in frozen donor oocyte IVF cycles in this study. Intracytoplamic sperm injection and "oocyte quality" likely mitigate some of the effects of male variables on outcomes following cryopreserved oocyte donation.
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http://dx.doi.org/10.1016/j.fertnstert.2018.06.003DOI Listing
October 2018

Early Detection of Ovarian Dysfunction by Anti-Mullerian Hormone in Adolescent and Young Adult-Aged Survivors of Childhood Cancer.

J Adolesc Young Adult Oncol 2019 02 3;8(1):18-25. Epub 2018 Oct 3.

1 Division of Endocrinology, Department of Pediatrics, Emory University, Atlanta, Georgia.

Purpose: Current guidelines recommend screening at-risk childhood cancer survivors for ovarian dysfunction using follicle-stimulating hormone (FSH). However, FSH identifies diminished ovarian reserve (DOR), a component of ovarian dysfunction, in the later stages when fertility preservation is less likely to succeed. This analysis evaluates the utility of anti-Mullerian hormone (AMH) for the assessment of DOR in adolescent and young adult (AYA)-aged survivors of childhood cancer.

Methods: A retrospective chart review of 13- to 21-year-old female survivors who received gonadotoxic therapy and were ≥2 years off therapy was performed. Gonadotoxic treatments were categorized as low, moderate, or high risk for future infertility. Patients with AMH below the assay's age-specific normal range were identified and stratified by FSH values (normal ≤12 mIU/mL). Prevalence of low AMH and AMH-FSH subgroups was calculated and risk factors were evaluated using logistic regression.

Results: AMH was measured in 190 survivors who received gonadotoxic treatment; of them, 35.3% had low AMH. Among survivors who received <30 Gy cranial radiation and were not on hormone therapy (n = 141), 18.4% had normal FSH with low AMH. Stratified by future infertility risk, 10.6% of low-risk, 38.1% of moderate-risk, and 25.7% of high-risk survivors had normal FSH with low AMH (p < 0.01). Within the low-risk group, normal FSH with low AMH was significantly associated with older age at diagnosis (p = 0.02).

Conclusion: Nearly 20% of AYA-aged at-risk survivors had low AMH and normal FSH. DOR in these patients would have been missed in standard recommended surveillance practices.
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http://dx.doi.org/10.1089/jayao.2018.0080DOI Listing
February 2019

Fertility preservation options in transgender people: A review.

Rev Endocr Metab Disord 2018 09;19(3):231-242

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

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.
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http://dx.doi.org/10.1007/s11154-018-9462-3DOI Listing
September 2018

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

Paediatr Perinat Epidemiol 2018 05 8;32(3):225-234. Epub 2018 Mar 8.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

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 (E 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr).

Results: Total thyroxine (T ) concentrations were positively associated with Pd3G and E 3G. Women with higher (vs lower) T had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T , respectively) and greater follicular phase maximum E 3G (E 3G = 41.7 ng/mg Cr for women with high T vs E 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T , 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.
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http://dx.doi.org/10.1111/ppe.12462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980701PMC
May 2018

Impact of cancer treatment on risk of infertility and diminished ovarian reserve in women with polycystic ovary syndrome.

Fertil Steril 2018 03 7;109(3):516-525.e1. Epub 2018 Feb 7.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Objective: To compare markers of fertility and ovarian reserve between cancer survivors and cancer-free women with and without polycystic ovary syndrome (PCOS).

Design: Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women's Study-a population-based cohort study.

Setting: Not applicable.

Patient(s): Female cancer survivors (n = 1,090) aged 22-45 years, diagnosed between ages 20 and 35 years, and at least 2 years after diagnosis; 369 participated in a clinic visit. Three hundred seventy-four reproductive-aged women without cancer also completed a clinic visit.

Intervention(s): None.

Main Outcome Measure(s): Infertility, time to first pregnancy after cancer diagnosis, and measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC]).

Results: Seventy-eight cancer survivors (7.2%) reported a PCOS diagnosis, with 41 receiving gonadotoxic treatment. Survivors with PCOS exposed to gonadotoxic treatment (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.2-4.5) and unexposed (OR 3.4, 95% CI 1.7-6.9) were more likely to report infertility than unexposed survivors without PCOS and were more likely to have fewer children than desired (exposed: OR 2.1, 95% CI 1.0-4.2; unexposed: OR 3.0, 95% CI 1.4-6.8). After adjusting for age, comparison women with PCOS had the highest markers of ovarian reserve (AMH: 2.43 ng/mL, 95% CI 1.22-4.82 ng/mL; AFC: 20.7, 95% CI 15.3-27.8), and cancer survivors without PCOS treated with gonadotoxic agents had the lowest levels (AMH: 0.19 ng/mL, 95% CI 0.14-0.26 ng/mL; AFC: 7.4, 95% CI 6.4-8.5).

Conclusion(s): Despite having higher AMH and AFC on average after cancer treatment, cancer survivors with PCOS were less likely to meet their reproductive goals compared with survivors without PCOS.
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http://dx.doi.org/10.1016/j.fertnstert.2017.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866226PMC
March 2018

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

Int J Cancer 2017 12 24;141(11):2187-2196. Epub 2017 Aug 24.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.

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.
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http://dx.doi.org/10.1002/ijc.30914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766343PMC
December 2017

Urban-Rural Differences in Tubal Ligation Incidence in the State of Georgia, USA.

J Rural Health 2018 03 21;34(2):122-131. Epub 2017 Jul 21.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Purpose: To evaluate the difference in tubal ligation use between rural and urban counties in the state of Georgia, USA.

Methods: The study population included 2,160 women aged 22-45. All participants completed a detailed interview on their reproductive histories. County of residence was categorized using the National Center for Health Statistics Urban-Rural Classification Scheme. We estimated the association between urbanization of county of residence and tubal ligation using Cox regression. Among women with a tubal ligation, we examined factors associated with prior contraception use and the desire for more children.

Findings: After adjustment for covariates, women residing in rural counties had twice the incidence rate of tubal ligation compared with women in large metropolitan counties (adjusted hazard ratio [aHR] = 2.0, 95% CI = 1.4-2.9) and were on average 3 years younger at the time of the procedure. No differences were observed between small metropolitan and large metropolitan counties (aHR = 1.1, CI = 0.9-1.5). Our data suggest that women from large metropolitan counties are slightly more likely than women from rural counties to use hormonal contraception or long-acting reversible contraception prior to tubal ligation and to desire more children after tubal ligation.

Conclusions: Women from rural counties are more likely to undergo a tubal ligation than their urban counterparts. Our results suggest that circumstances regarding opting for tubal ligation may differ between urban and rural areas, and recommendations of alternative contraceptive options may need to be tailored differently for rural areas.
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http://dx.doi.org/10.1111/jrh.12259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776071PMC
March 2018

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

Am J Epidemiol 2018 02;187(2):337-346

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

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.
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http://dx.doi.org/10.1093/aje/kwx240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860354PMC
February 2018

Human endometrial stromal cell plasticity: Reversible sFlt1 expression negatively coincides with decidualization.

Hypertens Pregnancy 2017 May 11;36(2):204-211. Epub 2017 May 11.

b Department of Gynecology and Obstetrics , Emory University School of Medicine , Atlanta , Georgia , USA.

Preeclampsia (PE) is a major complication of pregnancy in which the placenta is known to have shallow implantation into the uterine decidua. Studies have implicated soluble fms-like tyrosine kinase-1 (sFlt1), a soluble vascular endothelial growth factor (VEGF) receptor protein, in the pathogenesis of PE. sFlt1 has the ability to bind to and neutralize the angiogenic functions of VEGF and placental growth factor (PlGF). The presence of sFlt1 and its action in the endometrium is yet to be determined. We hypothesize that endometrial stromal cells (ESC) at the maternal-fetal interface may play a role in sFlt-1 regulation during pregnancy. In this study, we seek to understand the dynamic regulation of sFlt1 production in primary human ESC as a result of hormone stimulation and withdrawal. To mimic a biphasic menstrual cycle, ESC were treated with cAMP to induce endometrial decidualization that occurs during the luteal secretory phase, followed by cAMP withdrawal reflecting the follicular proliferative phase. Here, we present data to show that (1) ESC produce detectable amounts of sFlt1, (2) sFlt1 expression is turned off during decidualization at both the protein and RNA level (3) ESC decidualization and resulting sFlt1 expression are reversible phenomenon, and (4) Decidualization markers prolactin (PRL) and VEGF expressions in ESC are negatively correlated with sFlt1. These findings may have important implications in diseases such as PE that involve abnormal decidualization, implantation and angiogenesis at the maternal-fetal interface.
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http://dx.doi.org/10.1080/10641955.2017.1299172DOI Listing
May 2017

Impact of tamoxifen therapy on fertility in breast cancer survivors.

Fertil Steril 2017 01 22;107(1):243-252.e5. Epub 2016 Nov 22.

Department of Epidemiology, Rollins School of Public Health, Atlanta, Georgia.

Objective: To determine whether tamoxifen use is associated with decreased ovarian reserve and decreased likelihood of having a child after a breast cancer diagnosis, using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women Study.

Design: Population-based cohort study.

Setting: Not applicable.

Patient(s): Three hundred ninety-seven female breast cancer survivors aged 22-45 years whose cancer was diagnosed between ages 20 and 35 years and who were at least 2 years after diagnosis; 108 survivors also participated in a clinic visit.

Intervention(s): None.

Main Outcome Measure(s): Time to first child after cancer diagnosis, clinical measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC]) after cancer.

Result(s): Women who had ever used tamoxifen were substantially less likely to have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95% confidence interval [CI], 0.16, 0.54) than women who had never used tamoxifen. After adjusting for age at diagnosis, exposure to an alkylating agent, and race, the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential confounders, women who had used tamoxifen had an estimated geometric mean AMH level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken tamoxifen. Antral follicle count was also higher in the tamoxifen group compared with the tamoxifen nonusers when adjusted for the same variables (risk ratio 1.21; 95% CI, 0.84, 1.73).

Conclusion(s): Breast cancer survivors who had used tamoxifen were less likely to have a child after breast cancer diagnosis compared with survivors who never used tamoxifen. However, tamoxifen users did not have decreased ovarian reserve compared with the tamoxifen nonusers.
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http://dx.doi.org/10.1016/j.fertnstert.2016.10.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203952PMC
January 2017

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

J Inherit Metab Dis 2017 03 17;40(2):171-176. Epub 2016 Nov 17.

Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s10545-016-9990-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306419PMC
March 2017

Characteristics related to early secondary amenorrhoea and pregnancy among women diagnosed with systemic lupus erythematosus: an analysis using the GOAL study.

Lupus Sci Med 2016 22;3(1):e000139. Epub 2016 Sep 22.

Department of Rheumatology , Emory University School of Medicine , Atlanta, Georgia , USA.

Objective: Systemic lupus erythematosus (SLE) disproportionately affects women and often develops during their reproductive years. Research suggests that some women who receive cyclophosphamide as treatment for SLE experience earlier decline in menstrual function, but reproductive health among women with SLE who have not taken this drug is less well understood. This study aims to better understand the relation between SLE and reproduction by assessing early secondary amenorrhoea and pregnancy in women treated with and without cyclophosphamide from a population-based cohort with large numbers of African-Americans.

Methods: Female patients with SLE, ages 20-40 at time of diagnosis, who were 40 years or older at the time of the survey were included in this analysis (N=147). Participants in the Georgians Organized Against Lupus (GOAL) study were asked about their reproductive histories including early secondary amenorrhoea, defined as loss of menstruation before age 40.

Results: Women who were cyclophosphamide naïve had an increased prevalence of early secondary amenorrhoea compared with population estimates, 13-17% compared with 1-5%. Factors associated with early secondary amenorrhoea in women not treated with cyclophosphamide were marital status and receipt of a kidney transplant. Treatment with cyclophosphamide doubled the prevalence after adjustment for patient characteristics. Over 88% of women reported being pregnant at least once, and about 83% of these had a child, but the majority of pregnancies occurred before diagnosis.

Conclusions: SLE diagnosed in early adulthood may affect women's reproductive health even if they are not treated with cyclophosphamide. Better understanding of other factors related to reproductive health in this population will improve clinicians' and patients' abilities to make treatment and family planning decisions.
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http://dx.doi.org/10.1136/lupus-2015-000139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051470PMC
September 2016

Which female cancer patients fail to receive fertility counseling before treatment in the state of Georgia?

Fertil Steril 2016 Dec 24;106(7):1763-1771.e1. Epub 2016 Sep 24.

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia.

Objective: To assess which characteristics are associated with failure to receive fertility counseling among a cohort of young women diagnosed with cancer.

Design: Population-based cohort study.

Setting: Not applicable.

Patient(s): A total of 1,282 cancer survivors, of whom 1,116 met the inclusion criteria for the analysis.

Intervention(s): None.

Main Outcome Measure(s): The main outcome in this study was whether or not women reported receiving any information at the time of their cancer diagnosis on how cancer treatment might affect their ability to become pregnant.

Result(s): Forty percent of cancer survivors reported that they did not receive fertility counseling at the time of cancer diagnosis. Women were more likely to fail to receive counseling if they had only a high school education or less or if they had given birth. Cancer-related variables that were associated with a lack of counseling included not receiving chemotherapy as part of treatment and diagnosis with certain cancer types.

Conclusion(s): Counseling about the risk of infertility and available fertility preservation options is important to cancer patients. Additionally, counseling can make women aware of other adverse reproductive outcomes, such as early menopause and its associated symptoms. Less-educated women and parous women are at particular risk of not getting fertility-related information. Programs that focus on training not just the oncologist, but also other health care providers involved with cancer care, to provide fertility counseling may help to expand access.
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http://dx.doi.org/10.1016/j.fertnstert.2016.08.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136299PMC
December 2016

Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI).

Menopause 2016 09;23(9):993-9

1Division of Reproductive Endocrinology and Infertility2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA.

Objective: Approximately 20% of women with a premutation in the FMR1 gene experience primary ovarian insufficiency (POI). We explored diagnostic patterns, frequency of appropriate hormone replacement, obstetric outcomes, fertility treatment, reproductive decisions, and counseling of women with fragile X-associated POI (FXPOI).

Methods: Semistructured interviews with 79 women with FXPOI were conducted by a single interviewer. FMR1 cytosine-guanine-guanine repeat size was determined from a blood, saliva, or buccal sample.

Results: The median age of POI onset for women in our study was 33 years. Seventy-two percent of the women had an FMR1 cytosine-guanine-guanine repeat length of 80 to 100. Mean length of time from symptom onset to POI diagnosis was 1.12 years, longer in women with a younger age of POI onset and shorter in women who knew they were carriers. After diagnosis, 52% of women never took hormone therapy, started it years after POI diagnosis, or stopped it before 45 years of age. Forty-nine percent of the women had infertility, but 75% had had at least one genetically related child. Obstetric outcomes were similar to the general population. Forty-six percent of women had a diagnosis of low bone mineral density or osteoporosis, and an additional 19% had never had a bone density assessment.

Conclusions: Women with FXPOI are at significant risk for delayed POI diagnosis and undertreatment with hormone therapy. Although approximately 50% of women had infertility, most were able to conceive at least one child and had no elevated risk of adverse obstetric outcomes.
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http://dx.doi.org/10.1097/GME.0000000000000658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998843PMC
September 2016

Differences in Women's Use of Medical Help for Becoming Pregnant by the Level of Urbanization of County of Residence in Georgia.

J Rural Health 2017 01 14;33(1):41-49. Epub 2016 Jan 14.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Purpose: Our goal was to determine if there are differences by place of residence in visiting a doctor for help getting pregnant in a population-based study.

Methods: Using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women's Study, a cohort study of fertility outcomes in reproductive-aged women in Georgia, we fit models to estimate the association between geographic type of residence and seeking help for becoming pregnant.

Findings: The prevalence of visiting a doctor for help getting pregnant ranged from 13% to 17% across geographic groups. Women living in suburban counties were most likely to seek medical care for help getting pregnant compared with women living in urbanized counties (adjusted prevalence ratio (aPR) = 1.14, 95% CI: 0.74-1.75); among women who reported infertility this difference was more pronounced (aPR = 1.59, 95% CI: 1.00-2.53). Women living in rural counties were equally likely to seek fertility care compared with women in urbanized counties in the full sample and among women who experienced infertility.

Conclusions: Women living in urban and rural counties were least likely to seek infertility care, suggesting that factors including but not limited to physical proximity to providers are influencing utilization of this type of care. Increased communication about reproductive goals and infertility care available to meet these goals by providers who women see for regular care may help address these barriers.
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http://dx.doi.org/10.1111/jrh.12172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945485PMC
January 2017

Menses resumption after cancer treatment-induced amenorrhea occurs early or not at all.

Fertil Steril 2016 Mar 1;105(3):765-772.e4. Epub 2015 Dec 1.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Objective: To identify factors associated with cancer treatment-induced amenorrhea and time to return of menses.

Design: Population-based cohort study.

Setting: Not applicable.

Patient(s): Female cancer survivors who were diagnosed with cancer between the ages of 20 and 35 and were at least 2 years postdiagnosis at the time of recruitment (median = 7 years; interquartile range, 5-11).

Intervention(s): None.

Main Outcome Measure(s): Amenorrhea (≥6 months without menses) and resumption of menses.

Result(s): After excluding women with hysterectomies before cancer diagnosis, 1,043 women were eligible for analysis. Amenorrhea occurred in 31.6% of women. Among women treated with chemotherapy (n = 596), older age at diagnosis (30-35 vs. 20-24 years: adjusted odds ratio [aOR] = 2.37; 95% confidence interval [CI], 1.30, 4.30) and nulligravidity (vs. gravid: aOR = 1.50; 95% CI, 1.02, 2.21) were risk factors for amenorrhea. Among amenorrheic women, menses resumed in most (70.0%), and resumption occurred within 2 years of treatment for 90.0% of women. Survivors of breast cancer were more likely to resume menses at times greater than 1 year compared with lymphoma and pelvic-area cancers. Women diagnosed at older ages, those exposed to chemotherapy, and those exposed to any radiation experienced longer times to return of menses. Women who were older at diagnosis were more likely to have irregular cycles when menses returned.

Conclusion(s): Treatment-induced amenorrhea is common in cancer survivors, although most women resume menses within 2 years. However, once resumed, older women are more likely to have irregular cycles. Age at diagnosis and pregnancy history affect the risk of amenorrhea.
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http://dx.doi.org/10.1016/j.fertnstert.2015.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779728PMC
March 2016

Hypothyroidism after cancer and the ability to meet reproductive goals among a cohort of young adult female cancer survivors.

Fertil Steril 2016 Jan 30;105(1):202-7.e1-2. Epub 2015 Oct 30.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Objective: To determine whether developing hypothyroidism after cancer treatment is associated with a decreased probability of women being able to meet their reproductive goals.

Design: A population-based cohort study.

Setting: Not applicable.

Patient(s): A total of 1,282 cancer survivors, of whom 904 met the inclusion criteria for the analysis.

Intervention(s): None.

Main Outcome Measure(s): Three outcomes that may indicate reduced fertility, which include failure to achieve desired family size, childlessness, and not achieving pregnancy after at least 6 months of regular unprotected intercourse.

Result(s): We used data from the Furthering Understanding of Cancer Health and Survivorship in Adult (FUCHSIA) Women's Study to examine the association between being diagnosed with hypothyroidism after cancer and meeting reproductive goals. After adjusting for age and other potential confounders, women reporting hypothyroidism after cancer treatment were twice as likely to fail to achieve their desired family size (adjusted odds ratio [aOR] 1.91; 95% confidence interval [CI], 1.09, 3.33) and be childless (aOR 2.13; 95% CI, 1.25, 3.65). They were also more likely to report having unprotected intercourse for at least 6 months without conceiving (aOR 1.37; 95% CI, 0.66, 2.83).

Conclusion(s): Although cancer treatments themselves are gonadotoxic, it is important to consider other medical conditions such as hypothyroidism that occur after cancer treatment when counseling patients on the risks for impaired fertility or a shortened reproductive window.
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http://dx.doi.org/10.1016/j.fertnstert.2015.09.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710540PMC
January 2016

Racial Disparities in Seeking Care for Help Getting Pregnant.

Paediatr Perinat Epidemiol 2015 Sep 22;29(5):416-25. Epub 2015 Jul 22.

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA.

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.
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http://dx.doi.org/10.1111/ppe.12210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630798PMC
September 2015

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

Blood Cells Mol Dis 2015 Jun 31;55(1):56-61. Epub 2015 Mar 31.

Emory University School of Medicine, Department of Pediatrics, Division of Endocrinology and Metabolism, 2015 Uppergate Drive, NE Atlanta, GA 30322, USA; Division of Hematology/Oncology/BMT and Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, 2015 Uppergate Drive, NE Atlanta, GA 30322, USA.

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/Sβ(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.
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http://dx.doi.org/10.1016/j.bcmd.2015.03.012DOI Listing
June 2015