Disparities in the use of assisted reproductive technologies after breast cancer: a population-based study.

PURPOSE: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied. METHODS: To describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18-45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use-including oocyte/embryo cryopreservation or embryo transfer-after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART use. RESULTS: Among 36,468 women with invasive breast cancer, 206 (0.56%) used ART. Women significantly less likely to use ART were age 36-45 years at diagnosis (vs. 18-35 years: PR = 0.17, 95% CI 0.13-0.22); non-Hispanic Black or Hispanic (vs. non-Hispanic White: PR = 0.31, 95% CI 0.21-0.46); had at least one child (vs. no children: adjusted PR [aPR] = 0.39, 95% CI 0.25-0.60); or lived in non-urban areas (vs. urban: aPR = 0.28, 95% CI 0.10-0.75), whereas women more likely to use ART lived in high-SES areas (vs. low-/middle-SES areas: aPR = 2.93, 95% CI 2.04-4.20) or had private insurance (vs. public/other insurance: aPR = 2.95, 95% CI 1.59-5.49). CONCLUSION: Women with breast cancer who are socially or economically disadvantaged, or who already had a child, are substantially less likely to use ART after diagnosis. The implementation of policies or programs targeting more equitable access to fertility services for women with cancer is warranted.

Disparities in Fertility-Sparing Treatment and Use of Assisted Reproductive Technology After a Diagnosis of Cervical, Ovarian, or Endometrial Cancer.

OBJECTIVE: To assess the presence of sociodemographic and clinical disparities in fertility-sparing treatment and assisted reproductive technology (ART) use among patients with a history of cervical, endometrial, or ovarian cancer. METHODS: We conducted a population-based cohort study of patients aged 18-45 years who were diagnosed with cervical cancer (stage IA, IB), endometrial cancer (grade 1, stage IA, IB), or ovarian cancer (stage IA, IC) between January 1, 2000, and December 31, 2015, using linked data from the CCR (California Cancer Registry), the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. The primary outcome was receipt of fertility-sparing treatment , defined as surgical or medical treatment to preserve the uterus and at least one ovary. The secondary outcome was fertility preservation , defined as ART use after cancer diagnosis. Multivariable logistic regression analysis was used to estimate odds ratios and 95% CIs for the association between fertility-sparing treatment and exposures of interest: age at diagnosis, race and ethnicity, health insurance, socioeconomic status, rurality, and parity. RESULTS: We identified 7,736 patients who were diagnosed with cervical, endometrial, or ovarian cancer with eligible histology. There were 850 (18.8%) fertility-sparing procedures among 4,521 cases of cervical cancer, 108 (7.2%) among 1,504 cases of endometrial cancer, and 741 (43.3%) among 1,711 cases of ovarian cancer. Analyses demonstrated nonuniform patterns of sociodemographic disparities by cancer type for fertility-sparing treatment, and ART. Fertility-sparing treatment was more likely among young patients, overall, and of those in racial and ethnic minority groups among survivors of cervical and ovarian cancer. Use of ART was low (n=52) and was associated with a non-Hispanic White race and ethnicity designation, being of younger age (18-35 years), and having private insurance. CONCLUSION: This study demonstrates that clinical and sociodemographic disparities exist in the receipt of fertility-sparing treatment and ART use among patients with a history of cervical, endometrial, or ovarian cancer.

Survival outcomes following pregnancy or assisted reproductive technologies after breast cancer: A population-based study.

BACKGROUND: This study sought to determine the impact of pregnancy or assisted reproductive technologies (ART) on breast-cancer-specific survival among breast cancer survivors. METHODS: The authors performed a cohort study using a novel data linkage from the California Cancer Registry, the California birth cohort, and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System data sets. They performed risk-set matching in women with stages I-III breast cancer diagnosed between 2000 and 2012. For each pregnant woman, comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics were matched at the time of pregnancy. After matching, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pregnancy with breast-cancer-specific survival. We repeated these analyses for women who received ART. RESULTS: Among 30,021 women with breast cancer, 553 had a pregnancy and 189 attempted at least one cycle of ART. In Cox proportional hazards modeling, the pregnancy group had a higher 5-year disease-specific survival rate; 95.6% in the pregnancy group and 90.6% in the nonpregnant group (HR, 0.43; 95% CI, 0.24-0.77). In women with hormone receptor-positive cancer, we found similar results (HR, 0.43; 95% CI, 0.2-0.91). In the ART analysis, there was no difference in survival between groups; the 5-year disease-specific survival rate was 96.9% in the ART group and 94.1% in the non-ART group (HR, 0.44; 95% CI, 0.17-1.13). CONCLUSION: Pregnancy and ART are not associated with worse survival in women with breast cancer. LAY SUMMARY: We sought to determine the impact of pregnancy or assisted reproductive technologies (ART) among breast cancer survivors. We performed a study of 30,021 women by linking available data from California and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. For each pregnant woman, we matched at the time of pregnancy comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics. We repeated these analyses for women who received ART. We found that pregnancy and ART were not associated with worse survival.

Outcomes of the First Pregnancy After Fertility-Sparing Surgery for Early-Stage Cervical Cancer.

OBJECTIVE: To evaluate outcomes of the first pregnancy after fertility-sparing surgery in patients with early-stage cervical cancer. METHODS: We performed a population-based study of women aged 18-45 years with a history of stage I cervical cancer reported to the 2000-2012 California Cancer Registry. Data were linked to the OSHPD (California Office of Statewide Health Planning and Development) birth and discharge data sets. We included patients with cervical cancer who conceived at least 3 months after a fertility-sparing surgery, which included cervical conization or loop electrosurgical excision procedure. Those undergoing trachelectomy were excluded. The primary outcome was preterm birth. Secondary outcomes included growth restriction, neonatal morbidity, stillbirth, cesarean delivery, and severe maternal morbidity. We used propensity scores to match similar women from two groups in a 1:2 ratio of case group participants to control group participants: population individuals without cancer and individuals with cervical cancer (women who delivered before their cervical cancer diagnosis). Wald statistics and logistic regressions were used to evaluate outcomes. RESULTS: Of 4,087 patients with cervical cancer, 118 (2.9%) conceived after fertility-sparing surgery, and 107 met inclusion criteria and were matched to control group participants. Squamous cell carcinoma was the most common histology (63.2%), followed by adenocarcinoma (30.8%). Patients in the case group had higher odds of preterm birth before 37 weeks of gestation compared with both control groups (21.5% vs 9.3%, odds ratio [OR] 2.7, 95% CI 1.4-5.1; 21.5% vs 12.7%, OR 1.9, 95% CI 1.0-3.6), but not preterm birth before 32 weeks. Neonatal morbidity was more common among the patients in the case group relative to those in the cervical cancer control group (15.9% vs 6.9%, OR 2.5, 95% CI 1.2-5.5). There were no differences in rates of growth restriction, stillbirth, cesarean delivery, and maternal morbidity. CONCLUSION: In a population-based cohort, patients who conceived after surgery for cervical cancer had higher odds of preterm delivery compared with control groups.

Outcomes of the First Pregnancy After Fertility-Sparing Surgery for Early-Stage Ovarian Cancer.

OBJECTIVE: To evaluate the outcomes of the first pregnancy after fertility-sparing surgery in patients treated for early-stage ovarian cancer. METHODS: We performed a retrospective study of women aged 18-45 years with a history of stage IA or IC ovarian cancer reported to the California Cancer Registry for the years 2000-2012. These data were linked to the 2000-2012 California Office of Statewide Health Planning and Development birth and discharge data sets to ascertain oncologic characteristics and obstetric outcomes. We included in the case group ovarian cancer patients who conceived at least 3 months after fertility-sparing surgery. The primary outcome was preterm birth, and only the first pregnancy after cancer diagnosis was considered. Secondary outcomes included small-for-gestational-age (SGA) neonates, neonatal morbidity (respiratory support within 72 hours after birth, hypoxic-ischemic encephalopathy, seizures, infection, meconium aspiration syndrome, birth trauma, and intracranial or subgaleal hemorrhage), and severe maternal morbidity as defined by the Centers for Disease Control and Prevention. Propensity scores were used to match women in a 1:2 ratio for the case group and the control group. Wald statistics and logistic regressions were used to evaluate outcomes. RESULTS: A total of 153 patients who conceived after fertility-sparing surgery were matched to 306 women in a control group. Histologic types included epithelial (55%), germ-cell (37%), and sex-cord stromal (7%). Treatment for ovarian cancer was not associated with preterm birth before 37 weeks of gestation (13.7% vs 11.4%; odds ratio [OR] 1.23, 95% CI 0.69-2.20), SGA neonates (birth weight less than the 10th percentile: 11.8% vs 12.7%; OR 0.91, 95% CI 0.50-1.66), severe maternal morbidity (2.6% vs 1.3%; OR 2.03, 95% CI 0.50-8.25), or neonatal morbidity (both 5.9% OR 1.00, 95% CI 0.44-2.28). CONCLUSION: Patients who conceived at least 3 months after surgery for early-stage ovarian cancer did not have an increased risk of adverse obstetric outcomes.

Use of fertility preservation services in male reproductive-aged cancer patients.

While fertility preservation is a major concern among reproductive age cancer patients, little is known about access and use of fertility preserving services. We examined use of fertility preserving services among men with common solid tumors. A total of 3648 men age 18-40 including 2610 (71.6%) with testicular cancer, 939 (25.7%) with colorectal and 99 (2.7%) with prostate cancer were identified. Fertility preservation services were utilized in 9.3% of men overall including 4.1% who underwent fertility evaluation only and 7.8% who had a fertility preservation procedure. The rate of fertility preservation services rose from 6.6% (95%CI, 3.2-10.0) in 2008 to 12.4% (95%CI, 7.3-17.5) in 2017 (P = 0.04). Use of fertility preservation service was more common in patients with testicular (11.6%, aRR = 3.31; 95% CI 2.22-4.92) and prostate cancer (6.1%, aRR = 3.14; 95% CI 1.28-7.70) compared to those with colon cancer (3.4%). Younger men were more likely to utilize fertility preservation services. 11.5% of men age ≤ 35 years vs. 5.2% of men 36-40 used these services (P < 0.0001). Fertility preservation services were used in 10.8% of those who received chemotherapy (aRR = 1.81; 95% CI, 1.45-2.27) and in 8.1% of those who received radiation (aRR = 1.30 95% CI, 0.98-1.73). Medicaid patients were less likely to receive fertility preservation services than those with commercial insurance (0.7% vs. 10.1%; aRR = 11.58, 95%CI 2.10-63.69). These data indicate that while use of fertility preserving services is increasing, overall use of services is low among reproductive age males with cancer.

Outcomes after Fertility-sparing Surgery for Women with Ovarian Cancer: A Systematic Review of the Literature.

OBJECTIVE: To compare reproductive and oncologic outcomes of patients diagnosed with early-stage epithelial ovarian carcinoma, borderline ovarian tumors, or nonepithelial ovarian carcinoma according to receipt of fertility-sparing surgery or conventional surgery. DATA SOURCES: PubMed was searched from January 1, 1995, to May 29, 2020. METHODS OF STUDY SELECTION: Studies were included if they (1) enrolled women of childbearing age diagnosed with ovarian cancer between the ages of 18 years and 50 years, (2) reported on oncologic and/or reproductive outcomes after fertility-sparing surgery for ovarian cancer, and (3) included at least 20 patients. TABULATION, INTEGRATION, AND RESULTS: The initial search identified 995 studies. After duplicates were removed, we abstracted 980 unique citations. Of those screened, 167 publications were identified as potentially relevant, and evaluated for inclusion and exclusion criteria. The final review included 44 studies in epithelial ovarian cancer, 42 in borderline ovarian tumors, and 31 in nonepithelial ovarian carcinoma. The narrative synthesis demonstrated that overall survival does not seem to be compromised in patients undergoing fertility-sparing surgery compared with those undergoing conventional surgery, although long-term data are limited. Areas of controversy include safety of fertility-sparing surgery in the setting of high-risk factors (stage IC, grade 3, and clear cell histology), as well as type of surgery (salpingo-oophorectomy vs cystectomy). It seems that although there may be some fertility compromise after surgery, pregnancy and live-birth rates are encouraging. CONCLUSION: Fertility-sparing surgery is safe and feasible in women with early-stage low-risk ovarian cancer. Pregnancy outcomes for these patients also seem to be similar to those of the general population.

Triple stimulation (TriStim) before bilateral oophorectomy in a young woman with ovarian cancer: a case report and review of the literature.

BACKGROUND: Double ovarian stimulation (DuoStim) involves two rounds of controlled ovarian stimulation (COS) and oocyte retrieval in immediate succession. It represents a promising approach to increase oocyte yield for patients with diminished ovarian reserve or those with limited time before fertility-threatening oncologic treatment. We report the case of a 31-year-old woman with Stage IC endometrioid ovarian cancer who underwent a triple stimulation or "TriStim," completing three rounds of COS and oocyte retrieval within 42 days prior to bilateral salpingo-oophorectomy. CASE PRESENTATION: A 31 year old nulligravid woman presented for fertility preservation counseling following a bilateral ovarian cystectomy that revealed Stage IC endometroid adenocarcinoma arising within endometrioid borderline tumors. The patient was counseled for bilateral salpingo-oophorectomy, lymph node dissection, and omentectomy followed by three cycles of carboplatin/paclitaxel. Prior to this, all within six weeks, the patient underwent three rounds of controlled ovarian stimulation using an antagonist protocol and human chorionic gonadotropin (hCG) trigger, resulting in vitrification of nine two-pronuclear zygotes (2PN), after which definitive surgery was performed. CONCLUSIONS: Advantages of DuoStim procedures are increasingly recognized, especially for oncology patients with limited time before potentially sterilizing cancer treatment. To our knowledge, this is the first report of a triple stimulation ("TriStim"). Our case highlights that triple stimulation is a viable option for patients needing urgent fertility preservation in order to maximize egg and embryo yield within a limited time period.

Gender inequality in leadership and academic rank in academic reproductive endocrinology programs.

PURPOSE: To identify gender differences in leadership and academic rank within academic reproductive endocrinology (REI) programs with fellowships in the USA. METHODS: Official institutional websites of the 2017-2018 American Board of Obstetrics and Gynecology (ABOG)-accredited reproductive endocrinology fellowship programs were reviewed, and gender representation at each leadership position and academic rank (Division and Fellowship Director and Full, Associate, and Assistant Professor) was recorded. Univariate comparisons were performed using Chi-square tests, with significance at p < 0.05. RESULTS: Among 49 ABOG-accredited reproductive endocrinology programs, 263 faculty were identified, 129 (49.0%) male and 134 (51.0%) female. Division directors were 69.3% male and 30.7% female (p = 0.006). Similarly, fellowship directors were 65.3% male and 34.6% female (p = 0.03). Full professors (n = 101) were more frequently male (70.3% vs. 29.7%, p < 0.001). There was no difference in gender among associate professors (n = 60, 51.7% male vs. 48.3% female, p = 0.79), while significantly more assistant professors were female than male (n = 102, 73.6% vs. 26.4%, p < 0.001). CONCLUSION: While a majority of residents in obstetrics and gynecology and half of reproductive endocrinology academic faculty are female, women are still underrepresented among leadership positions and full professors in academic reproductive endocrinology programs with fellowship programs.

Hyperglycosylated human chorionic gonadotropin as a predictor of ongoing pregnancy.

BACKGROUND: Hyperglycosylated human chorionic gonadotropin, the predominant human chorionic gonadotropin variant secreted following implantation, is associated with trophoblast invasion. OBJECTIVE: To determine whether the initial serum hyperglycosylated human chorionic gonadotropin differs between ongoing and failed pregnancies, and to compare it to total serum human chorionic gonadotropin as a predictor of ongoing pregnancy. MATERIALS AND METHODS: Women undergoing fresh/frozen in vitro fertilization cycles at a university-based infertility clinic with an autologous day 5 single embryo transfer resulting in serum human chorionic gonadotropin >3 mIU/mL (n = 115) were included. Human chorionic gonadotropin was measured 11 days after embryo transfer in a single laboratory (coefficient of variation <6%). Surplus frozen serum (-80oC) was shipped to Quest Laboratories for measurement of hyperglycosylated human chorionic gonadotropin (coefficient of variation <9.1%). Linear regression analyses adjusted for oocyte age a priori were used to compare human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin in ongoing pregnancies (>8 weeks of gestation) and failed pregnancies (clinical pregnancy loss, biochemical and ectopic pregnancies). RESULTS: A total of 85 pregnancies (73.9%) were ongoing. Hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated (Pearson correlation coefficient 92.14, P < .0001), and mean values of both were positively correlated with blastocyst expansion score (P value test for trend < .0004). Mean human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin were significantly higher in ongoing vs failed pregnancies. Among ongoing pregnancies vs clinical losses, mean hyperglycosylated human chorionic gonadotropin, but not human chorionic gonadotropin, was significantly higher (19.0 vs 12.2 ng/mL, ß -8.1, 95% confidence interval -13.0 to -3.2), and hyperglycosylated human chorionic gonadotropin comprised a higher proportion of total human chorionic gonadotropin (4.6% vs 4.1%; risk ratio, 0.79; 95% confidence interval, 0.66-0.94). CONCLUSION: Measured 11 days after single blastocyst transfer, hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated, but only mean hyperglycosylated human chorionic gonadotropin and its ratio to total human chorionic gonadotropin were significantly higher in ongoing pregnancies vs clinical pregnancy losses. Further evaluation of hyperglycosylated human chorionic gonadotropin, including in multiple embryo transfers and multiple pregnancy, and using serial measurements, is required.

The effect of endometriosis on the antimüllerian hormone level in the infertile population.

PURPOSE: To determine whether the presence of endometriosis in infertile women without prior ovarian surgery influences markers of ovarian reserve, AMH and FSH. METHODS: A retrospective cohort study included three groups of women who presented for IVF treatment at our tertiary care center from 04/27/2015 to 05/31/2017: women with endometriosis and prior ovarian surgery (EnSx), women with endometriosis without prior ovarian surgery (En), and women with a primary diagnosis of male factor infertility (MF; reference group). RESULTS: There were 671 patients that met inclusion criteria (78 EnSx, 60 En, and 533 MF). Compared to the MF group (3.6 ± 3.0), a lower mean AMH level (ng/mL) was observed in the EnSx group (2.5 ± 2.5; aß - 1.21; 95% CI [- 1.79, -0.62]) and in the En group (2.5 ± 2.2; aß - 1.11; 95% CI [- 1.68, - 0.54]). Both endometriosis groups had a statistically significantly higher proportion of patients with an AMH < 1 (EnSx, 24.4%; OR, 2.39 [95% CI, 1.31, 4.36]; En, 28.3%; OR, 2.67 [95% CI, 1.41, 5.08]) compared to the MF group (13.9%). The mean baseline FSH level (lU/L) was statistically significantly higher in both endometriosis groups (EnSx, 8.6 ± 4.3; ß, 1.37 [95% CI, 0.39, 2.34]; En, 8.4 ± 3.7; ß, 0.96 [95% CI, 0.04, 1.87]) compared to the MF group (7.3 ± 2.2). CONCLUSIONS: Among infertility patients with endometriosis, with and without a history of ovarian surgery, ovarian reserve markers were worse (lower AMH and higher FSH) and a higher proportion had decreased ovarian reserve as measured by AMH compared to women with MF.

Diagnosis and management of a heterotopic pregnancy and ruptured rudimentary uterine horn.

BACKGROUND: Heterotopic pregnancies implanted in a rudimentary uterine horn account for 1 in 2-3 million gestations, and confer significant risk of morbidity due to uterine rupture and hemorrhage. CASE PRESENTATION: A 34-year-old nullipara presented with acute pelvic pain at 17 weeks of gestation with dichorionic-diamniotic twins, one in each horn of an anomalous uterus first diagnosed in pregnancy as bicornuate. Three-dimensional ultrasound and MRI revealed myometrial disruption in the left rudimentary uterine horn, and the patient underwent an uncomplicated abdominal hemi-hysterectomy. Fourteen days later, an uncomplicated dilation and curettage was performed for a fetal anomaly in the remaining twin in the right unicornuate uterus. CONCLUSION: This case demonstrates the utility of magnetic resonance imaging and three-dimensional ultrasound in the assessment of myometrial integrity in a gravid patient with a heterotopic pregnancy and ruptured rudimentary uterine horn. This case demonstrates the importance of pre-pregnancy diagnosis and management of mullerian anomalies.

Serum Human Chorionic Gonadotropin Among Women With and Without Obesity After Single Embryo Transfers.

Context: Serum human chorionic gonadotropin (hCG) levels are essential for diagnosing and monitoring early pregnancy. Obesity is a health care epidemic; however, the performance of this vital serum hormone in women with an elevated body mass index (BMI) is unknown. Objective: To investigate the association of BMI with serum hCG values and rate of hCG increase. Design: Retrospective cohort study. Setting: University-based infertility clinic. Patients: Women undergoing fresh vs frozen in vitro fertilization cycles with single-day three or five embryo transfers resulting in singleton live births (≥24 weeks' gestational age) from 2008 to 2015. Intervention(s): None. Main Outcome Measure(s): The initial hCG (mIU/mL, 16 days after oocyte retrieval) and 2-day percentage of hCG increases among BMI categories were compared using multivariable linear and logistic regression, adjusted a priori for the day of embryo transfer. Results: The initial serum hCG values correlated inversely with the BMI (P < 0.0001, test for trend). Low initial hCG values (<100 mIU/mL) were significantly more common across increasing BMI classes, from 1.4% of normal weight patients to 15.6% of those with a BMI ≥40 kg/m2 (P = 0.001, test for trend). The mean 2-day hCG increases were similar and normal (≥53%) across the BMI groups. Conclusions: Patients with obesity achieving live births had statistically significantly lower initial serum hCG values compared with patients who were nonobese. However, the mean 2-day percentage of increases in hCG were similar across BMI categories. The initial hCG values might lack sensitivity for live births in patients with obesity. The rate of hCG increase remains the mainstay of monitoring very early pregnancies after in vitro fertilization. Future studies should investigate whether serum analyte ranges should be adjusted according to the BMI.