Gestational Surrogacy: Consistent Laws are Necessary to Provide Effective Treatment

Cost-effectiveness analysis of uterus transplantation vs. gestational carrier for treatment of absolute uterine factor infertility in the United States.

Reassuring outcomes for single and coupled gay men using assisted reproductive technology

Safety of pregnancy after letrozole-FSH stimulation in breast cancer patients: a prospective comparison of frozen embryo transfer to self vs. gestational carriers

What are the medical, psychosocial and legal aspects of gestational surrogacy (GS), including pregnancy outcomes and complications, in a large series? Meticulous multidisciplinary teamwork, involving medical, legal and psychosocial input for both the intended parent(s) (IP) and the gestational carrier (GC), is critical to achieve a successful GS program. Small case series have described pregnancy rates of 17-50% for GS. There are no large case series and the medical, legal and psychological aspects of GS have not been addressed in most of these studies. To our knowledge, this is the largest reported GS case series. A retrospective cohort study was performed. Data were collected from 333 consecutive GC cycles between 1998 and 2012. There were 178 pregnancies achieved out of 333 stimulation cycles, including fresh and frozen transfers. The indications for a GC were divided into two groups. Those who have 'failed to carry', included women with recurrent implantation failure (RIF), recurrent pregnancy loss (RPL) and previous poor pregnancy outcome (n = 96; 132 cycles, pregnancy rate 50.0%). The second group consisted of those who 'cannot carry' including those with severe Asherman's syndrome, uterine malformations/uterine agenesis and maternal medical diseases (n = 108, 139 cycles, pregnancy rate 54.0%). A third group, of same-sex male couples and single men, were analyzed separately (n = 52, 62 cycles, pregnancy rate 59.7%). In 49.2% of cycles, autologous oocytes were used and 50.8% of cycles involved donor oocytes. The 'failed to carry' group consisted of 96 patients who underwent 132 cycles at a mean age of 40.3 years. There were 66 pregnancies (50.0%) with 17 miscarriages (25.8%) and 46 confirmed births (34.8%). The 'cannot carry pregnancy' group consisted of 108 patients who underwent 139 cycles at a mean age of 35.9 years. There were 75 pregnancies (54.0%) with 15 miscarriages (20.0%) and 56 confirmed births (40.3%). The pregnancy, miscarriage and live birth rates between the two groups were not significantly different (P = 0.54; 0.43; 0.38, respectively). Of the 178 pregnancies, 142 pregnancies were ongoing (surpassed 20 weeks) or had ended with a live birth and the other 36 pregnancies resulted in miscarriage (25.4%). Maternal (GS) complication rates were low, occurring in only 9.8% of pregnancies. Fetal anomalies occurred in only 1.8% of the babies born. Although it is a large series, the data are retrospective and conclusions must be drawn accordingly while considering bias, confounding and power. Due to the retrospective nature of this study, follow-up data on 6.3% of birth outcomes were incomplete. In addition, long-term follow-up data on GCs and IPs were not available to us at the time of publication. To our knowledge, this is the largest GS series published. We have included many details regarding not only the medical protocol but also the counseling and legal considerations, which are an inseparable part of the process. Data from this study can be included in discussions with future intended parents and gestational carriers regarding success rates and complications of GS.

Genetic offspring in patients with vaginal agenesis: Specific medical and legal issues

The effect of a history of a prior art live birth on subsequent live birth rates using linked art cycles

More Options for Fertility Preservation for Patients With Cancer.

Does BMI of gestational carriers (GCs) affect perinatal outcomes after embryo transfer? Overweight and class I obesity in GCs does not affect the rate of good perinatal outcomes. The use of GCs is increasing, but uniform guidance regarding optimal BMI for GCs is lacking. Women with obesity who conceive without fertility treatment or through autologous or donor in vitro fertilization are at higher risk of adverse maternal and fetal outcomes, but data on obesity in GCs are very limited. We performed a retrospective cohort study of 1121 GC cycles from January 2015 to December 2020 at US Fertility, the largest national partnership of fertility practices in the USA. All GC cycles performed at a large network of fertility practices were reviewed. Same-sex partners undergoing co-IVF were excluded. The primary outcome was good perinatal outcome from the first embryo transfer, defined as a singleton live birth at ≥37 weeks of gestation with birth weight between 2500 and 4000 g. Secondary outcome measures included frequencies of live birth, clinical pregnancy, miscarriage, full-term birth, low birth weight, large for gestational age, and cesarean delivery. A generalized linear model (log-binomial) was used for each to compare outcomes across BMI groups using normal BMI (20-24.9 kg/m2) as the reference group. Risk ratios and 95% CIs were estimated for each category group relative to normal BMI. We identified 1121 cycles in which GCs underwent first embryo transfer, of which 263 (23.5%) were in GCs with BMI >30. Demographics and reproductive history for GCs did not differ by BMI groups. The age of intended parents, use of frozen eggs, and fresh embryo transfers were higher with increasing BMI group. There were no statistically significant associations between BMI and good perinatal outcomes, live birth, clinical pregnancy, biochemical, spontaneous abortion, or low birth weight. However, among live births, higher BMI was significantly associated with birth by cesarean (P = 0.015) and large for gestational age infants (P = 0.023). This was a retrospective study, and there may be unmeasured confounders. The number of patients with BMI <20 or ≥35 was small, limiting the power for these groups. We were not able to assess all maternal and fetal outcomes. In this study, we did not identify any significant impact of BMI on the chances of having a good perinatal outcome. Prior research studies have been inconsistent and this is the largest study to date. No external funding was received for this work. The authors do not have any conflicts of interest to declare. N/A.

Shifting Surrogacy Laws and Legal Parenthood

Gestational carrier pregnancy outcomes from frozen embryo transfer depending on the number of embryos transferred and preimplantation genetic testing: a retrospective analysis

Background: Forkhead box protein A1 (FOXA1) plays a key role in determining estrogen receptor (ER) function and mammary ductal development and may repress the basal cell phenotype during differentiation of breast epithelium. While reproductive factors are known to influence breast cancer risk depending on the subtypes, data on the association of tumor FOXA1 protein expression and reproductive characteristics are very limited. Methods: Tissue microarrays comprising surgical tumors from 638 women (466 African-American [AA] and 172 European-American [EA], aged 20-75 years) with primary breast cancer in the Women’s Circle of Health Study (WCHS) were analyzed for FOXA1 expression by immunohistochemistry and automated image analysis. In-person interviews were conducted to obtain data on demographics, medical and family histories, and reproductive and menstrual histories. Logistic regression was performed for FOXA1 positivity (&amp;gt;10% cells with strong staining) with menopausal status, age at menarche, age at first live birth, parity, and breastfeeding, adjusting for age at diagnosis, family history of breast cancer, and history of benign breast disease. Results: FOXA1 expression was higher in tumors from EA compared to those from AA women (80% vs. 70% positivity, P=0.011). FOXA1 expression was highly correlated with ER positivity (88% positive in ER+ and 26% in ER- breast cancer among AA women; 90% and 29% respectively among EA women; both P&amp;lt;0.001). Among AA women, a higher number of live births was associated with lower FOXA1 expression (odds ratio [OR]=0.45, 95% confidence interval [CI]=0.22-0.91 for 2 live births and OR=0.44, 95% CI=0.20-0.91 for ≥3 live births, versus nulliparous). However, the inverse association was not observed among EA women, potentially due to the small sample size. Conclusion: In AA women, a higher number of live births, which has been related to greater risk of ER- breast cancer, is associated with lower FOXA1 expression. Because FOXA1 promotes luminal and represses the basal differentiation, respectively, the effects of parity on expression of FOXA1 may be the link whereby it increases risk of ER- breast cancer. (Funding: NIH P01CA151135, R01CA100598, R01CA185623, P30CA072720, K07CA201334; US Army Medical Research and Material Command DAMD-17-01-1-0334; the Breast Cancer Research Foundation; and the Philip L. Hubbell family) Citation Format: Ting-Yuan David Cheng, Rochelle Payne Ondracek, Song Yao, Wiam Bshara, Thaer Khoury, Gary R. Zirpoli, Warren Davis, Elisa V. Bandera, Michael Higgins, Christine B. Ambrosone. Breast tumor FOXA1 protein expression and reproductive characteristics among African-American and European-American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4998. doi:10.1158/1538-7445.AM2017-4998

Introduction: Type 2 diabetes (T2D) is hypothesized to be a risk factor for breast cancer. Possible mechanisms include adverse effects of impaired glucose regulation on endogenous hormone levels and increased inflammation of adipose tissue, which may be favorable to breast epithelial cell transformation, tumor-related angiogenesis, and cancer cell invasion. Recent meta-analyses suggest that T2D may be associated with a 15-20% increase in risk, but whether that increase is due to residual confounding by body mass index (BMI) is uncertain. Further, few studies have reported results separately by estrogen receptor (ER) status of the tumor, none have had appreciable numbers of ER- cases, and the only previous report on the association in African American (AA) women analyzed all subtypes together. Methods: We used data from the prospective Black Women’s Health Study to examine the relation of T2D to incidence of invasive breast cancer, overall and by ER subtype, among 54,337 AA women free from T2D and breast cancer at baseline and followed for 20 years. Included were 1,851 incident breast cancer cases, with 468 classified as ER- and 914 as ER+; data on ER status were not available for 469 cases. Participants were asked about medical conditions on each biennial questionnaire. In a validation study, 95% of self-reports of diabetes were confirmed by medical records. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for breast cancer for women with T2D relative to women without T2D, controlling for age, family history of breast cancer, BMI at age 18, waist-hip ratio, years of education, and reproductive factors. Results: The multivariable IRR for T2D versus no diabetes was 1.20 (95% confidence interval 1.01-1.41) for all breast cancer, 1.42 (1.02-1.98) for ER- breast cancer, and 1.06 (0.83-1.36) for ER+ breast cancer. Most cases had had diabetes for at least five years before the breast cancer diagnosis. IRRs for ≥5 years duration of diabetes were 1.46 (1.02-2.07) for ER- and 1.08 (0.83-1.41) for ER+ breast cancer. Recent BMI was not associated with increased risk of either ER subtype and was not a confounder in the present analyses. BMI at age 18, which was inversely associated with breast cancer risk in this and other studies, was the only appreciable confounder; in multivariable models that did not control for BMI at age 18, IRRs were 1.37 (0.99-1.90) and 1.03 (0.81-1.33) for ER- and ER+ breast cancer, respectively. Conclusions: The findings suggest that AA women with T2D are at increased risk of ER- breast cancer. AA women are about two times as likely to be diagnosed with ER- breast cancer as are U.S. white women and also have a markedly higher prevalence of T2D. Their higher prevalence of diabetes may contribute to the disparity in incidence of ER- breast cancer. The next step will be to assess whether risk of ER- breast cancer among diabetic women differs according to how well the diabetes is controlled. Citation Format: Julie R. Palmer, Nelsy Castro-Webb, Kimberly A. Bertrand, Traci N. Bethea, Lynn Rosenberg. Type 2 diabetes and increased risk of estrogen receptor-negative breast cancer in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5286. doi:10.1158/1538-7445.AM2017-5286

Comparing gestational carrier with uterine transplantation in uterine-factor infertility: a cost-effectiveness analysis.

SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

How much does the uterus matter? Perinatal outcomes are improved when donor oocyte embryos are transferred to gestational carriers compared to intended parent recipients