M.P. Rosen

Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer.

The post‐treatment quality of life (QOL) impacts of receiving precancer‐treatment infertility counseling and of pursuing fertility preservation have not been described in large‐scale studies of reproductive age women with cancer.

The Polycystic Ovary Post-Rotterdam: A Common, Age-Dependent Finding in Ovulatory Women without Metabolic Significance

INTRODUCTION The age-specific prevalence of polycystic ovaries (PCO), as defined by the Rotterdam criteria, among normal ovulatory women, has not yet been reported. It is also uncertain whether these women differ from their peers in the hormonal or metabolic profile. METHODS A total of 262 ovulatory Caucasian women aged 25-45 yr, enrolled in a community-based ovarian aging study (OVA), underwent transvaginal ultrasound assessment of ovarian volume and antral follicle count (AFC) in the early follicular phase and were categorized as to whether they met the Rotterdam definition of PCO by AFC (≥12 in one ovary) and/or by volume (>10 cm(3) for one ovary). The effect of age on prevalence of PCO was assessed. Serum hormones and metabolic measures were compared between women meeting each element of the Rotterdam criterion and those without PCO using age-adjusted linear regressions. RESULTS The prevalence of PCO by AFC was 32% and decreased with age. Those with PCO by AFC had lower FSH; higher anti-Müllerian hormone, estrone, dehydroepiandrostenedione sulfate, and free androgen index; and slightly higher total testosterone than those without PCO. However, slightly higher body mass index and waist circumference were the only metabolic differences. Women with PCO by volume had higher anti-Müllerian hormone and free androgen index but did not differ in any other hormonal or metabolic parameter. DISCUSSION PCO is a common, age-dependent finding among ovulatory women. These women lack the metabolic abnormalities seen in PCO syndrome. Isolated PCO in an ovulatory woman is not an indication for metabolic evaluation.

Effective method for emergency fertility preservation: random-start controlled ovarian stimulation

OBJECTIVE To determine whether random-start controlled ovarian stimulation (COS), in which a patient is stimulated on presentation regardless of her menstrual-cycle phase, has outcomes similar to conventional early follicular phase-start COS for fertility preservation in cancer patients. DESIGN Retrospective cohort study. SETTING Academic medical center. PATIENT(S) Women recently diagnosed with cancer and in preparation for gonadotoxic therapy. INTERVENTION(S) Random- versus conventional-start COS. MAIN OUTCOME MEASURE(S) PRIMARY OUTCOME number of mature oocytes retrieved; secondary outcomes: pattern of follicular development, oocyte yield, and fertilization rate. RESULT(S) The number of total and mature oocytes retrieved, oocyte maturity rate, mature oocyte yield, and fertilization rates were similar in random- (n = 35) and conventional-start (n = 93) COS cycles. No superiority was noted when comparing COS started in the late follicular (n = 13) or luteal phase (n = 22). The addition of letrozole, in the case of estrogen-sensitive cancers, did not adversely affect COS outcomes or oocyte maturity and competence in either random- or conventional-start protocols. CONCLUSION(S) Random-start COS is as effective as conventional-start COS in fertility preservation. This protocol would minimize delays and allow more patients to undergo fertility preservation and still proceed with cancer treatment within 2-3 weeks.

Acute ovarian failure underestimates age‐specific reproductive impairment for young women undergoing chemotherapy for cancer

The authors sought to describe the age‐specific impact of infertility and early menopause after chemotherapy among reproductive age women with cancer.

Racial, Socioeconomic, and Demographic Disparities in Access to Fertility Preservation in Young Women Diagnosed with Cancer

This study seeks to examine the relation between sociodemographic characteristics and the utilization of fertility preservation services in reproductive age women diagnosed with cancer.

A quantitative assessment of follicle size on oocyte developmental competence

OBJECTIVE To quantitatively assess the impact of follicle size on oocyte maturation, fertilization, and embryo quality. DESIGN Prospective study. SETTING Academic medical center. PATIENT(S) Couples undergoing ovarian stimulation and in vitro fertilization (IVF). INTERVENTION(S) A total of 235 cycles were monitored prospectively, and 2934 oocytes were collected from five groups of follicle size. Repeated measures multivariate analyses were used to compare the smaller follicle sizes with the lead follicle. MAIN OUTCOME MEASURE(S) Oocyte maturation, fertilization, and embryo quality. RESULT(S) Compared with the lead follicular group (>18 mm), the odds of a mature oocyte from a 16 to 18 mm size follicle were 37% and declined progressively with each size. The odds of fertilization of oocytes from follicles 16 to 18 mm in size was 28% less than the lead group and decreased with each size. The rate of polyspermy with conventional insemination was increased for the smaller follicular groups (adjusted odds ratio = 2.37). Follicle size did not predict embryo cell number, but embryos from smaller follicles had a statistically significantly higher fragmentation compared with the lead group. CONCLUSION(S) The lead follicular group was most likely to have a mature oocyte that was capable of fertilization and best suited for development into a high-quality embryo. The smaller follicles were capable of producing metaphase II oocytes that could fertilize, but at rates approaching only 60% that of the lead follicular group.

Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin

BACKGROUND The LH surge promotes ovulation via activation of multiple signaling networks in the ovarian follicle. Studies in animal models have shown the importance of LH-induced activation of the epidermal growth factor (EGF)signaling network in critical peri-ovulatory events. We investigated the biological significance of regulatory mechanisms mediated by EGF-like growth factors during LH stimulation in humans. METHODS We characterized the EGF signaling network in mature human ovarian follicles using in vivo and in vitro approaches. Amphiregulin (AREG) levels were measured in 119 follicular fluid (FF) samples from IVF/ICSI patients. Biological activity of human FF was assessed using in vitro oocyte maturation, cumulus expansion and cell mitogenic assays. RESULTS AREG is the most abundant EGF-like growth factor accumulating in the FF of mature follicles of hCG-stimulated patients. No AREG was detected before the LH surge or before hCG stimulation of granulosa cells in vitro, demonstrating that the accumulation of AREG requires gonadotrophin stimulation. Epiregulin and betacellulin mRNA were detected in both human mural and cumulus granulosa cells, although at significantly lower levels than AREG. FF from stimulated follicles causes cumulus expansion and oocyte maturation in a reconstitution assay. Immunodepletion of AREG abolishes the ability of FF to stimulate expansion (P < 0.0001) and oocyte maturation (P < 0.05), confirming the biological activity of AREG. Conversely, mitogenic activity of FF remained after depletion of AREG, indicating that other mitogens accumulate in FF. FF from follicles yielding an immature germinal vesicle oocyte or from an oocyte that develops into an aberrant embryo contains lower AREG levels than that from follicles yielding a healthy oocyte (P = 0.008). CONCLUSIONS EGF-like growth factors play a role in critical peri-ovulatory events in humans, and AREG accumulation is a useful marker of gonadotrophin stimulation and oocyte competence.

Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic-based sample of women in northern California.

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are related to an increased lifetime risk of developing breast and ovarian cancer. Although risk‐reducing salpingo‐oophorectomy reduces the risk of both cancers, loss of fertility is a major concern. A recent study suggested an association between BRCA1 mutation and occult primary ovarian insufficiency. The objective of the current study was to determine whether BRCA1/2 mutation carriers have an earlier onset of natural menopause compared with unaffected women.

A characterization of the relationship of ovarian reserve markers with age

OBJECTIVE To identify markers of ovarian age that best match the pattern of oocyte loss seen in histology specimens. DESIGN Cross-sectional study. SETTING University. PATIENT(S) Caucasian women (n = 252) aged 25-45 years. INTERVENTION(S) none. MAIN OUTCOME MEASURE(S) The relationship between antral follicle count (AFC), antimüllerian hormone (AMH), inhibin B, FSH, and E(2) with age was estimated using the power model, which previously has been shown to most accurately describe oocyte loss in histologic specimens. The power model was fit to each marker and used to compare the rates of change at ages 30 and 40 with the histologic pattern. Among those markers following the pattern, R(2) was used to compare the degree of relationship with age. RESULT(S) Both AMH levels and AFC exhibited significant progressive declines with age. The average rates of loss per year for AFC and AMH were, respectively, -0.57 and -1.09 at age 30, and -1.33 and -3.06 at age 40. FSH, inhibin B, and E(2) did not exhibit progressive rates of change. The R(2) for AFC was 27.3% and for AMH was 22.7%. CONCLUSION(S) Only AFC and AMH follow the pattern of oocyte loss observed histologically. Although AMH may be more cost-effective, AFC is a slightly more accurate noninvasive measure for ovarian aging.

Ovarian stimulation in cancer patients

The patients referred for fertility preservation owing to a malignant disease do not represent the typical population of subfertile patients treated in IVF units. Cancer may affect multiple tissues throughout the body and can result in a variety of complications during controlled ovarian stimulation. Determination of the controlled ovarian stimulation protocol and gonadotropin dose for oocyte/embryo cryopreservation requires an individualized assessment. This review highlights the new protocols that are emerging to reduce time constraints and emphasizes management considerations to decrease complications.