Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort.

BACKGROUND: Previous studies have shown decreased pregnancy rates and early menopause in female cancer survivors; however, infertility rates and reproductive interventions have not been studied. We investigated infertility and time to pregnancy in female childhood cancer survivors, and analysed treatment characteristics associated with infertility and subsequent pregnancy. METHODS: The Childhood Cancer Survivor Study (CCSS) is a cohort study including 5 year cancer survivors from 26 Canadian and US institutions who were younger than 21 years at the time of diagnosis between Jan 1, 1970, and Dec 31, 1986, and a sibling control group. We included women aged 18-39 years who had ever been sexually active. We gathered demographic, medical, and reproductive data via a baseline questionnaire, and quantified exposure to alkylating agents and radiation therapy. Self-reported infertility, medical treatment for infertility, time to first pregnancy in survivors and siblings, and the risk of infertility in survivors by demographic, disease, and treatment variables were analysed. FINDINGS: 3531 survivors and 1366 female sibling controls who enrolled between Nov 3, 1992, and April 4, 2004, were included. Compared with their siblings, survivors had an increased risk (relative risk [RR] 1·48 [95% CI 1·23-1·78]; p<0·0001) of clinical infertility (ie, >1 year of attempts at conception without success), which was most pronounced at early reproductive ages (RR 2·92 [95% CI 1·18-7·20], p=0·020, in participants ≤24 years; 1·61 [1·05-2·48], p=0·029, in those aged 25-29 years; and 1·37 [1·11-1·69], p=0·0035, in those aged 30-40 years). Despite being equally likely to seek treatment for infertility, survivors were less likely than were their siblings to be prescribed drugs for treatment of infertility (0·57 [95% CI 0·46-0·70], p<0·0001). Increasing doses of uterine radiation and alkylating agent chemotherapy were strongly associated with infertility. Although survivors had an increased time to pregnancy compared with their siblings (p=0·032), 292 (64%) of 455 participants with self-reported clinical infertility achieved a pregnancy. INTERPRETATION: A more comprehensive understanding of infertility after cancer is crucial for counselling and decision making about future conception attempts and fertility preservation. FUNDING: National Cancer Institute, American Lebanese Syrian Associated Charities, Swim Across America.

Use and Effectiveness of Gonadotropin-Releasing Hormone Agonists for Prophylactic Menstrual Suppression in Postmenarchal Women Who Undergo Hematopoietic Cell Transplantation.

STUDY OBJECTIVE: To describe the rates of use and effectiveness of gonadotropin-releasing hormone (GnRH) agonists and other forms of hormonal menstrual suppression in prevention of vaginal bleeding among young women who underwent hematopoietic stem cell transplantation (HCT). DESIGN: Retrospective descriptive study. SETTING: University-based pediatric HCT practice. PARTICIPANTS: Fifty-five postmenarchal women who underwent HCT between 2004 and 2011. INTERVENTIONS: Administration of GnRH agonists or other forms of hormonal menstrual suppression. MAIN OUTCOME MEASURES: Rates of use of GnRH agonists and other forms of hormonal menstrual suppression, and rates and descriptions of vaginal bleeding. RESULTS: Forty-six of the 55 patients had experienced regular or irregular vaginal bleeding before HCT and were considered to be at risk for thrombocytopenia-associated menorrhagia. Forty of the 46 (87%) received hormonal menstrual suppression. Thirty-three patients were treated with a GnRH agonist, 4 with combined hormonal contraceptive pills, 1 with a combined hormonal contraceptive patch, 1 with depot medroxyprogesterone, and 1 with oral norethindrone. Twenty-nine of the 33 patients (88%) who received a GnRH agonist had complete amenorrhea during HCT and 4 of 33 (12%) experienced some degree of vaginal bleeding. CONCLUSION: GnRH agonists appear effective in prevention of vaginal bleeding complications in most postmenarchal women who underwent HCT. Some patients who might benefit do not receive a GnRH agonist and multiple barriers exist in identification and treatment of them.

Robot-assisted laparoscopic myomectomy and adenomyomectomy with a flexible CO2 laser device.

We describe a novel surgical technique combining the use of a robotic surgical platform with a flexible CO2 laser in gynecologic surgery at a university-hospital-based reproductive medicine practice. Thirteen women with symptomatic uterine fibroids and/or adenomyosis, desiring uterine conservation, underwent robot-assisted laparoscopic myomectomy or focal adenomyomectomy with CO2 laser energy using a novel flexible delivery fiber (BeamPath GYN-L fiber, OmniGuide, Cambridge, MA, USA). On average, four myomas or areas of adenomyosis were removed with an average total specimen weight of 95 g. The average operating time was 169 min and the average estimated blood loss was 25 mL. No perioperative complications were observed. Preliminary experience with robot-assisted minimally invasive gynecologic surgery utilizing a novel flexible CO2 laser fiber has comparable operative outcomes to those reported for conventional laparoscopic energy sources, and this technique appears safe. The minimal lateral thermal spread of photonic energy, combined with the enhanced precision allowed by a computer-based surgical platform, appears ideal for reproductive surgical applications.

Early ß-human chorionic gonadotropin trends in vanishing twin pregnancies.

OBJECTIVE: To describe the early ß-hCG trends in vanishing twins compared with normally progressing singleton and twin pregnancies. DESIGN: Retrospective cohort study. SETTING: University-based infertility clinic. PATIENT(S): Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 1998 and 2010. INTERVENTION(S): Early ß-hCG level increase in vanished twin pregnancies was compared with the level increase in normally progressing singleton and twin pregnancies. MAIN OUTCOME MEASURE(S): Two-day percent increase in ß-hCG level. RESULT(S): Pregnancies with vanishing twins demonstrated a significantly lower mean 2-day percent increase in ß-hCG level than singletons and twins (114.3% vs. 128.8% and 125.4%, respectively). Vanishing twins arresting at earlier developmental stages demonstrated significantly further reduced ß-hCG level increases. Infrequently, all groups had ß-hCG level increases less than previously established clinical thresholds that led to a live birth. CONCLUSION(S): Early ß-hCG level increases are slower in vanishing twins than in singleton and twin pregnancies, with the slowest increases seen when the spontaneous fetal losses occur at earlier developmental stages. All increases, however, are within clinically accepted normal limits. Therefore, abnormal ß-hCG level increases should not be attributed to a vanishing twin. Of note, an abnormal ß-hCG level trend--even an initial decrease--does not preclude live birth, even in a singleton pregnancy.

Public opinion regarding utilization of assisted reproductive technology (ART) in obese women.

BACKGROUND: There have been calls to restrict access to fertility treatment in women above a certain body mass index (BMI). It is important to consider public expectations before formulating policy. The study objective was to assess public opinion regarding provision of assisted reproductive technology (ART) to obese (BMI>30 kg/m(2)) women in the United States. The study was conducted through an Internet-based survey of U.S. residents ages 18-75. METHODS: Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to describe predictors of response based on demographic characteristics. RESULTS: Of the 1049 respondents, 60.7% support the use of ART in obese women. Adjusting for age and gender, the odds of support were over twice as high in participants with BMI>40 kg/m(2) as in normal-weight respondents (OR=2.87, 95% CI=1.28-6.44). Fifty-five percent of participants supported a BMI limit for access to ART. Both increasing education (p-value=0.02) and BMI (p-value=0.01) were inversely associated with support of a BMI limit. Individuals who had themselves used ART were also less likely (OR=0.27, 95% CI=0.07--0.99) to support a BMI limit. CONCLUSIONS: In an Internet-based survey, participants who are in favor of ART are likely to support its use among obese women. More than 50% of these respondents also support implementation of a BMI limit for access to these services.

Female cancer survivors are low responders and have reduced success compared with other patients undergoing assisted reproductive technologies.

OBJECTIVE: To investigate the effect of prior chemotherapy and radiation on assisted reproductive technology (ART) outcomes. DESIGN: Retrospective cohort study. SETTING: University-based infertility clinic. PATIENT(S): Female cancer survivors who had received chemotherapy or radiation and all other women undergoing first-fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S): Survivors' ART outcomes were compared with all women undergoing first-fresh IVF/ICSI cycles and those with male-factor infertility only. Multivariate logistic and Poisson regression analyses were used to estimate the effect of cancer therapy on ART outcomes. MAIN OUTCOMES MEASURE(S): Number of oocytes retrieved and embryos obtained; odds of cycle cancelation, clinical pregnancy, and live birth. RESULT(S): Compared with others undergoing IVF/ICSI, survivors had significantly fewer oocytes retrieved and embryos available for transfer. In addition, survivors were significantly more likely to be canceled (odds ratio [OR] 5.60, 95% CI 2.94-10.66) and had lower pregnancy and live birth rates (OR 0.30, 95% CI 0.13-0.68; and OR 0.27, 95% CI 0.10-0.69; respectively). Odds ratios were stronger when the comparison group was restricted to those with male-factor infertility only. CONCLUSION(S): Women who have received systemic therapy for malignancy should be considered to be low responders and counseled that their per-cycle live birth rate is lower than that of their peers. These data strongly support offering fertility preservation before cancer therapy when possible.

Population-based study of attitudes toward posthumous reproduction.

OBJECTIVE: To measure public attitudes toward posthumous reproduction. DESIGN: Cross-sectional study. SETTING: Electronic survey. PATIENT(S): A total of 1,049 men and women living in the United States between the ages of 18 and 75 years. INTERVENTION(S): Multiple-choice questionnaire. MAIN OUTCOME MEASURE(S): Descriptive statistics regarding support for posthumous reproduction, such as regarding emergency harvesting of gametes, and attitudes toward consent; multivariable analyses of demographic and personal experiences associated with support for posthumous reproduction. RESULT(S): Results showed that 47.8% supported and 31.1% opposed retrieving gametes from men, and 42.7% supported and 35.9% opposed retrieving gametes from women. The remainder was undecided. Among supporters, 69.8% believed prior consent from the deceased was required. Support was positively associated with younger age, higher education, higher income, Democratic political party affiliation, history of infertility, and currently attempting conception. Gender, religion, race, and region of the country were not associated with support. Organ donors and those who support IVF were more likely to support posthumous reproduction (odds ratio [95% confidence interval] 1.68 [1.19-2.38] and 12.30 [6.56-23.04], respectively). Most respondents were initially unfamiliar with posthumous reproduction. CONCLUSION(S): Almost 50% of the general population support posthumous reproduction in men and women. The majority favored prior consent from the deceased. These data caution against emergency gamete harvesting without prior consent.

Transabdominal follicular aspiration for oocyte retrieval in patients with ovaries inaccessible by transvaginal ultrasound.

OBJECTIVE: To investigate the efficacy of ultrasound-guided transabdominal follicular aspiration when the ovaries are not accessible transvaginally. DESIGN: Retrospective case-control study. SETTING: University-hospital based in vitro fertilization (IVF) clinic. PATIENT(S): 69 women undergoing transabdominal follicular aspiration for oocyte retrieval, including 12 cases of mixed abdominal/vaginal aspiration, compared with controls matched by age, follicle number, and year of procedure undergoing standard transvaginal aspiration. INTERVENTION(S): Transabdominal follicular aspiration when one or more ovaries could not be retrieved via standard transvaginal aspiration. MAIN OUTCOME MEASURE(S): Total and mature oocytes retrieved, damaged oocytes, fertilization rate, embryo number and quality, and clinical and ongoing pregnancy rates. RESULT(S): Cases of transabdominal aspiration had slightly fewer oocytes retrieved, but no statistically significant differences were found for damaged oocytes, fertilization rates, embryo number and quality, or pregnancy rates. In 12 years, one complication requiring hospitalization was noted. CONCLUSION(S): This study demonstrates that transabdominal ultrasound-guided follicular aspiration is safe and efficacious, yielding clinical results in women with significant ovarian displacement, comparable with results achieved by transvaginal aspiration in women with normally positioned ovaries. Transabdominal ultrasound-guided aspiration should be the modality of choice when the ovaries are not accessible transvaginally.

Multivariate analysis of the association between oocyte donor characteristics, including basal follicle stimulating hormone (FSH) and age, and IVF cycle outcomes.

OBJECTIVE: To determine whether oocyte donor FSH and age are independently associated IVF cycle success. DESIGN: Retrospective cohort study. SETTING: University hospital-based IVF clinic. PATIENT(S): Three hundred twelve donor/recipient pairs undergoing oocyte donation IVF. MAIN OUTCOME MEASURE(S): Number of mature oocytes and embryos, clinical pregnancy, and live birth rates. RESULT(S): Donors' basal FSH levels were not associated with IVF cycle outcomes. However, for every year increase in donor age, the number of mature oocytes decreased by 0.39 and the number of embryos decreased by 0.25 resulting in 1 less embryo for each 4-year increase in age, even in young donors. For every 100 pg/mL increase in estradiol on the day of hCG administration, the number of mature oocytes increased by 0.49 and the number of embryos increased by 0.36. For each additional 75 IU of gonadotropin used during stimulation, the likelihood of pregnancy and live birth decreased by 3.5%. CONCLUSION(S): Donor oocyte IVF cycle outcomes were not associated with donor basal FSH. However, donor age and estradiol level on the day of hCG administration were significantly associated with numbers of mature oocytes and embryos obtained, and the amount of gonadotropin used in the stimulation was significantly associated with the likelihood of pregnancy and live birth.