J.L. Chan

Reproductive Decision-Making in Women with BRCA1/2 Mutations

Expanded genetic testing of BRCA mutations has led to identification of more reproductive-aged women who test positive for the mutation which might impact attitudes and decisions about relationships, childbearing and the use of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). A cross-sectional survey was administered to 1081 self-reported BRCA carriers to investigate how knowledge of BRCA status influences these issues. The mean age at BRCA test disclosure was 44xa0years and 36xa0% reported a personal history of cancer. Of 163 women who were unpartnered, 21.5xa0% felt more pressure to get married. Of 284 women whose families were not complete, 41xa0% reported that carrier status impacted their decision to have biological children. Women with a history of cancer were more likely to report that knowledge of BRCA+ status impacted their decision to have a child (OR 1.8, 95xa0% CI 1–3.2). Fifty-nine percent thought PGD should be offered to mutation carriers and 55.5xa0% thought PND should be offered. In conclusion, knowledge of BRCA status impacts attitudes regarding relationships and childbearing, and most carriers believe that PGD and PND should be offered to other carriers. This study suggests that BRCA carriers desire and would benefit from reproductive counseling after test disclosure.

Outcomes of ovarian stimulation after treatment with chemotherapy

PurposeChemotherapeutic agents have a known gonadotoxic effect; however, it is difficult to predict the impact they may have on ovarian stimulation. The objective of this study was to evaluate response to ovarian stimulation in patients exposed to chemotherapy compared with patients who were chemotherapy-naïve.MethodsA retrospective cohort study of 130 patients with cancer or autoimmune disease was performed. Demographics, ovarian reserve, ovarian response and stimulation parameters, and oocyte data were compared between patients who were pre- and post-chemotherapy. Logistic regression modeling was performed to identify risk factors for cancellation and low oocyte yield, adjusting for confounders as appropriate.ResultsAntral follicle count (AFC) was significantly lower in post-chemo patients (9 vs. 17, pu2009<u20090.001). Post-chemotherapy patients were more likely to be cancelled during stimulation (23 vs. 4xa0%, pu2009=u20090.003). Among those that went to retrieval, there was no difference in total number of oocytes (10 vs. 10, pu2009=u20090.31) or mature oocytes retrieved (8 vs. 8, pu2009=u20090.38), despite higher starting (300 vs. 450xa0IU, pu2009<u20090.001) and total gonadotropin (3075 vs. 4612.5xa0IU, pu2009=u20090.008) doses in post-chemotherapy patients. Low AFC (≤6) was associated with cycle cancellation (OR 7.7, 95xa0% CI 1.8–33.2) and low oocyte yield (<6) (OR 5.4, 95xa0% CI 1.6–17.7).ConclusionsPatients post-chemotherapy have lower AFC compared with the chemotherapy-naïve and have higher cancellation rates. Among those who underwent oocyte retrieval, oocyte yield was similar in both groups. Low AFC was most strongly associated with cycle cancellation and oocyte yield. Post-chemotherapy patients had higher rates of cycle cancellation but did equally well as pre-chemotherapy patients if they reached retrieval.

Fertility Sparing Surgery for Localized Ovarian Cancers Maintains an Ability to Conceive, but is Associated With Diminished Reproductive Potential

Little is known about fertility outcomes after fertility sparing surgery (FSS) for localized ovarian cancers.

Regret around fertility choices is decreased with pre-treatment counseling in gynecologic cancer patients

PurposeData have demonstrated an association between regret and lack of fertility counseling among patients undergoing treatment for non-gynecologic cancers. We sought to determine if fertility-related regret is reduced with pre-treatment counseling or fertility-sparing surgery (FSS) in patients with gynecologic cancers.MethodsA cross-sectional survey was administered to 593 reproductive-age survivors (18–40xa0years old at diagnosis) of localized cervix, ovarian, or endometrial cancers that were eligible for FSS. A validated decision regret score was used to evaluate regret in patients.ResultsFour hundred seventy women completed the survey. Forty-six percent received pre-treatment counseling about treatment’s effects on fertility. Having received counseling (adjusted ß-coefficient of −1.24, 95xa0% CIu2009=u2009−2.29 to −0.18, pu2009=u20090.02), satisfactory counseling (adjusted ß-coefficient of −2.71, 95xa0% CIu2009=u2009−3.86 to −1.57, pu2009<u20090.001), and FSS (adjusted ß-coefficient of −1.26, 95xa0% CIu2009=u2009−2.39 to −0.14, pu2009=u20090.03) were associated with lower regret post-treatment, after adjusting for age. Time since diagnosis, prior parity, socioeconomic status and cancer type were not associated with regret (pu2009>u20090.05). While 50xa0% of women reported desiring more children after diagnosis, desire for children after treatment was associated with increased regret (adjusted ß-coefficient of 3.97, 95xa0% CIu2009=u20092.92–5.02, pu2009<u20090.001).ConclusionsThough less than half of study participants received counseling about the effect of cancer treatment on future fertility, both fertility counseling and FSS were associated with decreased regret in reproductive-aged women with gynecologic cancers. The desire for more children after treatment was associated with increased regret.Implications for cancer survivorsInquiring about fertility desires and providing counseling regarding reproductive outcomes following cancer treatment should be implemented as part of the treatment process.

Oncofertility for women with gynecologic malignancies

The emerging field of oncofertility addresses fertility and the reproductive health needs for cancer patients, a key topic in cancer survivorship. Given that the standard treatment for gynecologic malignancies involves removal of reproductive organs, pelvic radiation, or chemotherapy, the effect of such treatment on fertility and options for fertility preservation are even more relevant than for other malignancies. In young women with new diagnoses of cervical, endometrial, or ovarian cancers, viable strategies for fertility preservation without compromising oncological outcome exist and should be considered. We present here a comprehensive review of the literature as it pertains to gynecologic malignancies on 1) the effects of radiation and chemotherapy on fertility, 2) fertility-sparing surgeries and the role of assisted reproductive technology, and 3) fertility preservation in adolescent girls and women with BRCA germline mutations.

Sexual satisfaction and quality of life in survivors of localized cervical and ovarian cancers following fertility-sparing surgery

OBJECTIVEnTo determine if sexual satisfaction and sexual quality of life (QOL) are different in survivors of localized cervical and ovarian cancers who undergo fertility-sparing surgery (FSS) as compared with standard surgery.nnnMETHODSn470 survivors of localized cervical and ovarian cancers diagnosed between the ages of 18-40 were recruited from the California Cancer Registry to complete a cross-sectional survey. Validated questionnaires were used to assess sexual satisfaction and sexual QOL.nnnRESULTSn228 women with localized cervical cancer and 125 with localized ovarian cancer completed the survey. In the cervical cancer group, 92 underwent FSS. Compared with the 84 women who did not undergo FSS (had a hysterectomy, but retained at least one ovary), there was no significant difference in sexual satisfaction or sexual QOL mean scores in women who maintained their uterus (cold-knife cone or trachelectomy), after controlling for age and menopausal status. 82 women with ovarian cancer underwent FSS. Compared with the 39 women that had a bilateral salpingo-oophorectomy, we found no significant differences in sexual satisfaction or sexual QOL in women who maintained at least one ovary (USO or cystectomy), after controlling for age and menopausal status.nnnCONCLUSIONSnWhile FSS may allow for post-treatment fertility, it may not confer a significant benefit with regard to sexual satisfaction or sexual QOL. Thus, the decision to perform FSS should not be dictated based on preservation of sexual functioning.

Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: a regional cross-sectional study

BACKGROUND: Polycystic ovary syndrome is a heterogeneous disorder and its presentation varies with race and ethnicity. Reproductive‐age women with polycystic ovary syndrome are at increased risk of metabolic syndrome; however, it is not clear if prevalence of metabolic syndrome and clustering of its components differs based on race and ethnicity. Moreover, the majority of these women do not undergo routine screening for metabolic syndrome. OBJECTIVE: We sought to compare the prevalence of metabolic syndrome and clustering of its components in women with polycystic ovary syndrome in the United States with women in India, Brazil, Finland, and Norway. STUDY DESIGN: This is a cross‐sectional study performed in 1089 women with polycystic ovary syndrome from 1999 through 2016 in 5 outpatient clinics in the United States, India, Brazil, Finland, and Norway. Polycystic ovary syndrome was defined by the Rotterdam criteria. Main outcome measures were: metabolic syndrome prevalence, blood pressure, body mass index, fasting high‐density lipoprotein cholesterol, fasting triglycerides, and fasting glucose. Data from all sites were reevaluated for appropriate application of diagnostic criteria for polycystic ovary syndrome, identification of polycystic ovary syndrome phenotype, and complete metabolic workup. The US White women with polycystic ovary syndrome were used as the referent group. Logistic regression models were used to evaluate associations between race and metabolic syndrome prevalence and its components and to adjust for potential confounders, including age and body mass index. RESULTS: The median age of the entire cohort was 28 years. Women from India had the highest mean Ferriman‐Gallwey score for clinical hyperandrogenism (15.6 ± 6.5, P < .001). The age‐adjusted odds ratio for metabolic syndrome was highest in US Black women at 4.52 (95% confidence interval, 2.46–8.35) compared with US White women. When adjusted for age and body mass index, the prevalence was similar in the 2 groups. Significantly more Black women met body mass index and blood pressure criteria (P < .001), and fewer met fasting triglycerides criteria (P < .05). The age‐ and body mass index–adjusted prevalence of metabolic syndrome was highest in Indian women (odds ratio, 6.53; 95% confidence interval, 3.47–12.30) with abnormalities in glucose and fasting high‐density lipoprotein cholesterol criterion and in Norwegian women (odds ratio, 2.16; 95% confidence interval, 1.17–3.98) with abnormalities in blood pressure, glucose, and fasting high‐density lipoprotein cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence of metabolic syndrome and its components compared to US White women. CONCLUSION: Despite a unifying diagnosis of polycystic ovary syndrome, there are significant differences in the prevalence of metabolic syndrome and clustering of its components based on race and ethnicity, which may reflect contributions from both racial and environmental factors. Our findings indicate the prevalence of metabolic syndrome components varies in women with polycystic ovary syndrome, such that compared to White women from the United States, Black US women had the highest prevalence, whereas women from India and Norway had a higher prevalence of metabolic syndrome independent of obesity. The differences in clustering of components of metabolic syndrome based on ethnicity highlight the need to routinely perform complete metabolic screening to identify specific targets for cardiovascular risk reduction strategies in these reproductive‐age women.

Mode of conception does not affect fetal or placental growth parameters or ratios in early gestation or at delivery

PurposeRatio of fetal weight to placenta size varies by mode of conception (fertility treatments utilized) in animals. Our objective was to assess whether fertility treatments also affect these ratios in humans.MethodsIn this retrospective study, we assessed two cohorts: (a) early gestation cohort, women with singleton pregnancies who underwent first trimester vaginal ultrasound and (b) delivered cohort, women who delivered a live-born, singleton infant with placenta disposition to pathology. Crown rump length (CRL) and estimated placental volume (EPV) were calculated from first trimester ultrasound images using a validated computation. Infant birth weight (BW), pregnancy data, placental weight (PW), and placental histopathology were collected. Fetal growth-to-placental weight ratios (CRL/EPV; BW/PW) and placentas were compared by mode of conception. Linear regression was used to adjust for confounding variables.ResultsTwo thousand one hundred seventy patients were included in the early gestation cohort and 1443 in the delivered cohort. Of the early gestation cohort (a), 85.4% were spontaneous conceptions, 5.9% Non-IVF Fertility (NIFT), and 8.7% IVF. In the delivered cohort (b), 92.4% were spontaneous, 2.1% NIFT, and 80 5.5% IVF. There were no significant differences between fetal growth-to-placental weight parameters, ratios, and neonatal birth measurements based on mode of conception. Placenta accreta was significantly higher in the patients receiving fertility treatments (1.2 versus 3.6%, pu2009<u20090.05).ConclusionsMode of conception does not appear to influence fetal growth-to-placental weight ratios throughout gestation. In addition, findings in animal models may not always translate into human studies of infertility treatment outcomes.

Female Genomics: Infertility and Overall Health

Abstract Female infertility is a complex disease linked to multiple etiologies including genetic factors. Owing to the multifactorial nature of infertility, it is often difficult to identify single causative genes. Despite this challenge, investigations into the genetic causes of infertility have been performed to shed light on the etiology and for the possibility of developing personalized medical approaches to therapy. Multiple techniques have been utilized to better characterize the genetic origins of this disease, including genome‐wide association studies. We present here a review of the genetic causes of female infertility, detailing some of the more recent findings in the genetics of polycystic ovary syndrome, endometriosis, primary ovarian insufficiency, hypothalamic amenorrhea, leiomyomas, and Mullerian anomalies.