Sara E. Barton

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.

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.

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.

Early beta-human chorionic gonadotropin trends in vanishing twin pregnancies

OBJECTIVE To describe the early β-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 β-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 β-hCG level. RESULT(S) Pregnancies with vanishing twins demonstrated a significantly lower mean 2-day percent increase in β-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 β-hCG level increases. Infrequently, all groups had β-hCG level increases less than previously established clinical thresholds that led to a live birth. CONCLUSION(S) Early β-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 β-hCG level increases should not be attributed to a vanishing twin. Of note, an abnormal β-hCG level trend--even an initial decrease--does not preclude live birth, even in a singleton pregnancy.

Twin pregnancies with a ‘vanished’ embryo: a higher risk multiple gestation group?

BACKGROUND Prior studies have documented increased risks to the offspring of IVF singletons that result from a vanished twin pregnancy. We aim to investigate the effect on perinatal outcomes of having an early vanished triplet in IVF twins. METHODS This is a retrospective cohort study of twins from a large academic IVF practice. Multivariate analysis was performed to examine the perinatal risks--including small for gestational age (SGA), low-birthweight (LBW), preterm delivery and early preterm delivery--in twins that resulted from an early vanished triplet compared with twins without a vanished embryo. RESULTS Of 829 IVF twin deliveries, 59 were a result of vanished triplet pregnancies (7.1%). There was no significant increase in SGA, LBW or delivery <37 weeks in the vanished triplets compared with other twins; however, the risk of early preterm birth (<32 weeks) was significantly higher (OR 3.09, 95% CI 1.63-5.87) and the length of gestation of these pregnancies was on average 1.5 weeks shorter (P < 0.01). In addition, the unadjusted mean birthweight was lower by nearly 200 g in the vanished triplet pregnancies (P < 0.01). CONCLUSIONS IVF twin pregnancies with a vanished triplet are at an increased risk for early preterm birth compared with other twin pregnancies. These pregnancies should be recognized at higher risk for early preterm birth and considered for increased obstetrical monitoring. A significant limitation of this study is that the cause for preterm birth was unknown.

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.

Oocyte Retrieval and Embryo Transfer

Technical aspects of the oocyte retrieval and embryo transfer are critical to the success of an assisted reproductive technologies program. The clinician must be able to master challenging clinical situations, such as accessing ovaries in abnormal anatomic locations at oocyte retrieval and performing embryo transfer in the face of cervical stenosis. Anticipation of challenges, equipment selection and setup, and patient preparation are all critical in maximizing the likelihood of optimal outcomes.