Harry J. Lieman

Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women.

OBJECTIVE Our aim was to determine the effect of aging on the hypothalamic-pituitary-gonadal axis function. STUDY DESIGN We studied 9 women aged 25 to 40 years with well-defined idiopathic premature ovarian failure and compared them with 8 women aged 51 to 70 years who had age-appropriate menopause. All women underwent 24 hours of frequent blood sampling every 10 minutes before and after replacement with transdermal estradiol targeted to achieve serum concentrations of approximately 100 pg/ml. RESULTS In the absence of estrogen exposure, women with premature ovarian failure demonstrated a greater 24-hour mean luteinizing hormone concentration compared with that in the older women with age-appropriate menopause (32.3+/-4.3 mlU/ml vs 19.2+/-2.4 mlU/ml, p=0.0001). Despite the lesser luteinizing hormone serum levels in the older group, the luteinizing hormone pulse frequency per 24 hours was similar (22.1+/-3.0 pulses per 24 hours in prematurely menopausal women vs 21.9+/-2.5 pulses per 24 hours in the older postmenopausal women, p=0.94). When exposed to estrogen, mean luteinizing hormone concentrations decreased to 11.6+/-2.7 mlU/ml in prematurely menopausal women versus 4.4+/-1.0 mlU/ml in older postmenopausal women, p=0.017. Both groups had suppressed mean luteinizing hormone secretion compared with their paired, non-estradiol-exposed studies, p=0.0001. Frequency of luteinizing hormone pulsations was reduced to 16.5+/-3.5 pulses per 24 hours in prematurely menopausal women exposed to estradiol (p < 0.0058, compared with non-estradiol-exposed women). Further reduction was observed in older postmenopausal women (11.5+/-1.1 pulses per 24 hours, p=0.0001, compared with nonestradiol exposure, and p=0.0125, vs prematurely menopausal, estradiol-exposed women). Pulse amplitude was suppressed in both prematurely menopausal women (5.6+/-0.5 mlU/ml to 2.3+/-0.5 mlU/ml, p=0.0001) and older postmenopausal women (3.6+/-0.4 mlU/ml to 2.3+/-0.6 mlU/ml p=0.04) in the presence of estradiol. Although luteinizing hormone pulse amplitudes were greater in the women with premature menopause in the absence of estradiol (p=0.0028) compared with those in older postmenopausal women, pulse amplitudes became similar in the presence of estradiol. Parallel changes in mean follicle-stimulating hormone were observed. Women with premature ovarian failure had a mean follicle-stimulating hormone level of 71.1+/-9.4 mlU/ml that was suppressed to 18.0+/-4.1 mlU/ml after estradiol exposure (p=0.0001); values in older postmenopausal women were 45.9+/-6.0 and 10.3+/-2.0, respectively (p=0.0001). Although the women with premature ovarian failure secreted more follicle-stimulating hormone in the absence and presence of estradiol, only the former situation was statistically significant (p=0.0008 and p=0.23, respectively). CONCLUSIONS These data suggest that there is an age-related decrease in gonadotropin secretion that may be hypothalamic or pituitary in origin. There is less luteinizing hormone secreted in women older than age 50. There is greater suppression of luteinizing hormone and follicle-stimulating hormone secretion by estradiol in aged women. Thus these data indicate that postmenopausal hormone changes involve central hypothalamic-pituitary alterations, as well as ovarian changes.

Random anti-Müllerian hormone (AMH) is a predictor of ovarian response in women with elevated baseline early follicular follicle-stimulating hormone levels

OBJECTIVE To investigate the utility of random anti-Müllerian hormone (AMH) in assessing ovarian response among women with diminished ovarian reserve (DOR) diagnosed by elevated early follicular-phase FSH levels. DESIGN Retrospective study. SETTING Academic and academically affiliated assisted reproductive technology (ART) programs. PATIENT(S) Seventy-three women undergoing ART with elevated early follicular FSH levels. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Number of oocytes retrieved during ART cycle, number of day 3 embryos, and cycle cancellation and clinical pregnancy rates. RESULT(S) Random AMH levels were strongly correlated with the number of oocytes retrieved during an ART cycle among women with elevated FSH (r=0.55). Women with elevated FSH who had a random serum AMH level of 0.6 ng/mL or higher had twice the number of oocytes retrieved (11±1.3 vs. 5.6±0.6), a greater number of day 3 embryos (5.7±0.9 vs. 3±0.5), and approximately a third of the cycle cancellation rate (14% vs. 41%) compared with women with a random serum AMH below 0.6 ng/mL. The clinical pregnancy rate was also higher among women with a random serum AMH≥0.6 ng/mL (28% vs. 14%), however, the difference was not statistically significant. CONCLUSION(S) A random serum AMH level is useful in setting expectations for ART prognosis in women with elevated early follicular-phase serum FSH levels.

Elevated body mass index is associated with lower serum anti-mullerian hormone levels in infertile women with diminished ovarian reserve but not with normal ovarian reserve

OBJECTIVE To investigate the association between elevated body mass index (BMI) and ovarian reserve. DESIGN Cross-sectional study. SETTING Academic institutions. PATIENT(S) Two hundred ninety women with infertility. Diminished ovarian reserve (DOR) was defined as day 3 FSH>10 IU/L. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Random serum antimullerian hormone (AMH) levels and number of oocytes retrieved during assisted reproductive technology cycle. RESULT(S) Increasing BMI was associated with lower random serum AMH levels in infertile women with DOR but not in women with normal ovarian reserve (NOR). Among women with DOR, mean random serum AMH levels were 33% lower in overweight and obese women compared with women with normal weight. The same association was not true for women with NOR. Out of 290 women evaluated for infertility, 109 women underwent a controlled ovarian hyperstimulation (COH)-IVF cycle. Women with elevated BMI and DOR had lower number of oocytes retrieved compared with women with normal BMI and DOR (6.4±4.3 vs. 9.4±6), an association that was not observed among women with NOR. CONCLUSION(S) Overweight and obese women with DOR as defined by high day 3 serum FSH levels have lower serum AMH levels and number of oocytes retrieved compared with nonobese women with DOR.

Obesity adversely affects serum anti-müllerian hormone (AMH) levels in Caucasian women

ObjectivePrevious studies regarding the effect of obesity on serum anti-müllerian hormone (AMH) levels have been conflicting. Our aim was to determine the effect of obesity on serum AMH levels among women from different racial backgrounds.MethodsThe medical records of 350 women (159 Caucasian, 99 African-American, 58 Hispanic, 34 Asian with ages 16–46) evaluated for infertility at an academic-affiliated center and who had AMH levels measured as part of their evaluation were reviewed. Age, AMH, body mass index (BMI), self-reported race, etiology of infertility, smoking history, maximum serum early follicular follicle-stimulating hormone (FSH) levels, antral follicle count (AFC), and history of ovarian surgery, chemotherapy, or radiotherapy were recorded.ResultsAge correlated negatively with AMH and antral follicle count across all races (p < 0.05). After adjusting for age, polycystic ovary syndrome diagnosis, and smoking, elevated BMI had a negative correlation with AMH in Caucasian women (β = 0.17, p = 0.01) but not in African-American, Hispanic, or Asian women.ConclusionElevated BMI correlates negatively with AMH in Caucasian women but not in African-American, Hispanic, or Asian women. Additional studies are needed to elucidate further the effect of race on the interaction between obesity and ovarian reserve.

How many eggs are needed to produce an assisted reproductive technology baby: is more always better?

OBJECTIVE To evaluate the association between the number of mature (metaphase II [MII]) oocytes per assisted reproductive technology (ART) cycle and the likelihood of live birth. DESIGN Retrospective study. SETTING Academic infertility practice. PATIENT(S) Seven hundred thirty-seven infertile women undergoing their initial fresh embryo, nondonor IVF or intracytoplasmic sperm injection cycle at Montefiores Institute for Reproductive Medicine and Health between January 2002 and December 2008. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Live birth. RESULT(S) Two hundred twenty-four cycles resulted in a live birth (30.4%). Live birth cycles had significantly more MII oocytes obtained per cycle as compared with their unsuccessful counterparts (11.0 ± 5.9 vs. 9.7 ± 6.2, respectively). Multivariate logistic regression was done to determine the minimum number of MII oocytes per cycle as a predictor of live birth after adjustment for age and historical maximum FSH values. Cycles that included the average number of MII in this cohort were used as a reference group. For cycles with five or fewer MII oocytes obtained, there was a statistically significant decrease in the likelihood of a live birth as compared with the reference group (odds ratio 0.61, 95% confidence interval 0.38-0.99). However, cycles with six or fewer obtained MII oocytes were not less likely to result in a live birth when compared with the reference group (odds ratio 0.69, 95% confidence interval 0.45-1.08). CONCLUSION(S) In our cohort, there was an advantage to obtaining six or more MII oocytes during the fresh oocyte retrieval compared with five or fewer oocytes. There was not an advantage, however, to obtaining 10 or more or 15 or more oocytes as compared with obtaining 6-9 oocytes. The strategy of aiming for a greater number of oocytes in an ART cycle should be revisited.

Successful pregnancy after transient ovarian failure following treatment of symptomatic leiomyomata

OBJECTIVE To report a case of transient ovarian failure after treatment of symptomatic leiomyomata and review other iatrogenic causes of transient ovarian failure. DESIGN Case report and literature review. SETTING University-affiliated private practice. PATIENT(S) A 35-year-old woman with symptomatic leiomyomata. INTERVENTION(S) Bilateral uterine artery embolization with subsequent abdominal myomectomy to treat unchanged regular heavy menstrual flow. MAIN OUTCOME MEASURE(S) Ovarian function. RESULT(S) Because medical therapy failed to control her menorrhagia, the patient proceeded with uterine artery embolization. She had persistent menorrhagia after bilateral uterine artery embolization and underwent exploratory laparotomy and myomectomy. After surgery, she had amenorrhea, hot flushes, and elevated FSH levels for 3 months. Ovarian function recovered after a short course of oral contraceptives, and the patient conceived without assistance. CONCLUSION(S) Several interventions can affect normal ovarian function and can lead to permanent or transient ovarian failure. Possible causes of transient ovarian failure are radioactive iodine treatment, radiation, chemotherapy, pelvic surgery, stress, and uterine artery embolization. Before these interventions are applied, the possibility of ovarian failure and available preventive measures should be discussed with the patient.

Serum progesterone on the day of human chorionic gonadotropin administration predicts clinical pregnancy of sibling frozen embryos

OBJECTIVE To evaluate patient characteristics and fresh in vitro fertilization (IVF) cycle parameters that influence success of sibling frozen-thawed embryo transfer (FET) cycles. DESIGN Retrospective study. SETTING Academic infertility practice. PATIENT(S) Infertile women undergoing FET cycles using embryos cryopreserved on day 3 after insemination after an initial fresh IVF cycle. INTERVENTION(S) 90 FET cycles. MAIN OUTCOME MEASURE(S) Clinical pregnancy (CP). RESULT(S) The likelihood of CP after FET was statistically significantly higher in women who had achieved CP in the preceding fresh IVF cycle (71.4% vs. 40.6%). Multivariable logistic regression analysis confirmed that patients achieving CP after the fresh IVF cycle were more likely to achieve CP after FET (OR 5.5; 95% CI, 1.2-25.3) after adjusting for age, number, and cleavage status of embryos transferred. Additionally, higher serum levels of progesterone on the day of human chorionic gonadotropin administration emerged as predictive of CP after FET at a statistically significant level. CONCLUSION(S) The outcome of the fresh embryo transfer cycle is the foremost predictor of CP after FET of the sibling embryos. The relationship between serum progesterone on the day of human chorionic gonadotropin administration in the fresh cycle and the outcome of subsequent FET is noteworthy and merits further investigation.

Egg freezing, procreative liberty, and ICSI: the double standards confronting elective self-donation of oocytes

The consensus view among relevant professional societies opposing the offering of elective oocyte cryopreservation for potential future self-donation withstands neither clinical nor ethical scrutiny. The favorable risk-benefit ratio of this technology mandates both the prioritization of patient autonomy for informed women seeking to maximize-not guarantee-their chances of having genetically related children, and a justification for viewing egg freezing differently from intracytoplasmic sperm injection.

Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality.

Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested.

Acute eosinophilic pneumonia with intramuscular progesterone after in vitro fertilization

OBJECTIVE To report an unusual case of acute eosinophilic pneumonia that was associated with IM P in oil after IVF. DESIGN Case report. SETTING Academic teaching hospital. PATIENT(S) A 35-year-old primigravid female who developed acute eosinophilic pneumonia after administration of IM P in oil as luteal-phase support after IVF. INTERVENTION(S) Corticosteroid therapy; replacement of IM P with intravaginal preparation. MAIN OUTCOME MEASURE(S) Evaluation of blood eosinophil counts along with clinical symptoms and chest radiograph findings at initial presentation and throughout the hospital course. RESULT(S) After the noted interventions, there was a marked improvement of clinical symptoms, chest radiograph findings, and eosinophilia. CONCLUSION(S) Although allergic reactions to IM P-in-oil administration are exceedingly rare, clinicians caring for patients using these products should be aware of potential adverse reactions and subsequent management.