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PubMed1997

Leptin is inversely related to age at menarche in human females.

Over the last century there has been a trend toward an earlier onset of menarche attributed to better nutrition and body fatness. With the discovery of the obesity gene and its product, leptin, we reexamined this hypothesis from a new perspective. As delayed menarche and leanness are considered risk factors for osteoporosis, we also evaluated the relation between leptin and bone mass. Body composition and serum leptin levels were measured, and the timing of menarche was recorded in 343 pubertal females over 4 yr. Body composition was measured by dual x-ray absorptiometry, and leptin by a new RIA. All participants were premenarcheal at baseline (aged 8.3-13.1 yr). Leptin was strongly associated with body fat (r = 0.81; P < 0.0001) and change in body fat (r = 0.58; P < 0.0001). The rise in serum leptin concentration up to the level of 12.2 ng/mL (95% confidence interval, 7.2-16.7) was associated with the decline in age at menarche. An increase of 1 ng/mL in serum leptin lowered the age at menarche by 1 month. A serum leptin level of 12.2 ng/mL corresponded to a relative percent body fat of 29.7%, a body mass index of 22.3, and-body fat of 16.0 kg. A gain in body fat of 1 kg lowered the timing of menarche by 13 days. Leptin was positively related to bone area (r = 0.307; P < 0.0001) and change in bone area (r = 0.274; P < 0.0001). A critical blood leptin level is necessary to trigger reproductive ability in women, suggesting a threshold effect. Leptin is a mediator between adipose tissue and the gonads. Leptin may also mediate the effect of obesity on bone mass by influencing the periosteal envelope. This may have implications for the development of osteoporosis and osteoarthritis.

Adipose Tissue↗
PubMed1979

13, 14-dihydro-15-keto-prostaglandin F2alpha concentrations in human plasma and amniotic fluid.

An antiserum to 13,14-dihydro-15-keto-prostaglandin F2alpha (PGF2alphaM) was prepared and a radioimmunoassay evaluated in various reproductive states. PGF2alphaM plasma concentration was 63.6 +/- 10.3 pg/ml (mean +/- SEM) in cycling women. The concentration fluctuated throughout the menstrual cycle and pregnancy, but no discernible patterns were noted. PGF2alphaM concentrations were elevated at the time of urea + oxytocin induced abortion (238 +/- 54 pg/ml) and during late stages of normal labor (352 +/- 107 pg/ml) but were not elevated during labor prior to 7 cm dilatation. Following intra-amniotic instillation of 5 mg of PGF2alpha tromethamine into the amniotic sac, PGF2alphaM concentration increased in the amniotic fluid. In the plasma of these patients there was an eighteenfold rise in plasma PGF2alphaM concentration compared to a 3.5-fold rise in PGF2alpha at 1 hour, suggesting changes in PGF2alphaM may be more easily detected than the parent compound. While PGF2alphaM may be a useful index of PGF2alpha production, it appears that PGF2alphaM is of little value in predicting the occurrence of uterine contraction.

Abortion, Induced↗
PubMed2002

Predictors of ovulatory failure in women with epilepsy.

Women with epilepsy (WWE) are at increased risk for reproductive disorders. This study was designed to evaluate whether WWE are more likely to have anovulatory cycles and to assess the relative association of the epilepsy syndrome category and antiepileptic drugs (AEDs) to ovulatory dysfunction. Subjects included women aged 18 to 40 years not receiving hormones. Women without epilepsy (23 controls) and women with localization-related epilepsy (LRE, n = 59) or idiopathic (primary) generalized epilepsy (IGE, n = 35) receiving either a cytochrome P450 enzyme (cP450) inducing AED (carbamazepine, phenytoin, and phenobarbital), a cP450 inhibiting AED (valproate), or an AED that does not alter cP450 enzymes (lamotrigine and gabapentin) in monotherapy for 6 months or more were followed for three menstrual cycles. A transvaginal ovarian ultrasound was obtained. Endocrine and metabolic variables were measured and luteinizing hormone sampled over 8 hours on days 2 to 5 of one cycle. Anovulatory cycles occurred in 10.9% of cycles in controls, 14.3% of cycles with LRE, and 27.1% of cycles with IGE. Of women using valproate currently or within the preceding 3 years, 38.1% had at least one anovulatory cycle in contrast with 10.7% of women not using valproate within the preceding 3 years. Predictors of ovulatory failure included IGE syndrome, use of valproate currently or within 3 years, high free testosterone, and fewer numbers of luteinizing hormone pulses, but not polycystic-appearing ovaries. WWE are more likely to experience anovulatory menstrual cycles and the effects of epilepsy syndrome, and AED therapy may be additive. Women with IGE receiving valproate were at highest risk for anovulatory cycles, polycystic-appearing ovaries, elevated body mass index, and hyperandrogynism. WWE with anovulatory cycles may have no other signs of reproductive dysfunction. Therefore, clinicians must be alert to this potential complication of epilepsy.

Adolescent↗
PubMed1995

Comparison of parameters to study seasonality in reproductive outcome.

This report compares validity, precision and convenience of three frequently used parameters used to describe seasonality in reproductive outcome: prevalence, index and ratio observed versus expected. Each has its advantages and disadvantages; the choice of the parameter depends on the aim of the study. It is advisable to report the number of cases and referents per month, because all three parameters can be derived from this information.

Birth Rate↗
PubMedDate not supplied

Quantitative ultramorphological analysis of human sperm: fifteen years of experience in the diagnosis and management of male factor infertility.

The advantages of quantitative ultramorphological (QUM) sperm analysis in the diagnosis and treatment of male infertility are presented. The QUM methodology is based on three elements: complementary scanning electron microscopy and transmission electron microscopy observations of 7 sperm cell subcellular organelles (acrosome, postacrosomal lamina, nucleus, neck, axoneme, mitochondrial sheath, and outer dense fibers); systematic classification of the specific ultramorphological malformations into 4 pathological and the normal categories, indicating the morphological state of each subcellular organelle; and comparison between well-defined reference groups with opposite fertility status or treatment conditions. QUM has established 2 indices for the in vivo and in vitro male fertility potential: (1) Natural Fertility Index (NFI), with accurate prediction (97% sensitivity and 90% specificity) of 80% of the male patients; and (2) IVF score, with prediction of 76% of the nonfertilizing and 90% of fertilizing IVF groups. QUM has enabled assessment of ultramorphological indications for varicocele and radiation exposure. Varicocele causes defects in sperm head organelles related to early spermatid development, whereas ionizing radiation causes amorphous head shape. QUM established criteria for specific non-in-vitro therapeutic interventions, including varicocelectomy, follicle-stimulating hormone (FSH) administration, and acupuncture. The varicocele index enabled correct classification of 79 and 89% of patients with and without varicocele. Males with idiopathic impairment of sperm acrosome and nucleus are potential responders to FSH treatment, whereas patients exhibiting low sperm activity are candidates for acupuncture treatment. Patients with a low Natural Fertility Index are recommended for an assisted reproduction technique (ART). based on the ultramorphology of the tail axoneme. Patients who achieved pregnancy following intrauterine insemination or in vitro fertilization and those whose wives conceived only following intracytoplasmic sperm injection were classified with accuracy of 78 and 74%, respectively. QUM sperm analysis is clinically informative, nontraumatic, and cost-effective, and is recommended when the male infertility factor cannot be clearly diagnosed by routine tests prior to first ART trial.

Cell Nucleus↗
PubMed1987

Serum total and HDL cholesterols according to reproductive status in Japanese females.

In order to observe variations according to reproductive status, serum total cholesterol (TC) and HDL cholesterol (HDL-C) were investigated in 153 pregnant, in 153 age-adjusted non-pregnant females, in 787 females aged 45-54 years living in a northern suburb of Tokyo, and in 150 12-year-old girls from a private junior high school in a southern suburb of Tokyo. Non-menstruating (non-menarcheal, postmenopausal) females had significantly higher TC and significantly lower HDL-C/TC than menstruating (menarcheal, premenopausal) females did in both the age groups of 12 and 45-54 years, although no significant difference of HDL-C was found between them. The menstruating females tended to be more overweight in Quetelet's index and had thicker skinfolds. Pregnant females at the eighth month of gestation revealed a significantly high value of both TC and HDL-C vs age-adjusted non-pregnant females, while at the fourth month of gestation only HDL-C was high.

Adolescent↗
PubMed2006

Increasing trend of spina bifida and decreasing birth weight in relation to declining body-mass index of young women in Japan.

We analyzed the existing data from various surveys on the prevalence of spina bifida, birth weight, and body-mass index (BMI), dietary intake, and smoking habits of Japanese young women. We found that the increasing trend of the prevalence of spina bifida paralleled with the decrease in birth weight, and the decrease in BMI and dietary energy intake and the increase in smoking rate among women of childbearing age. The decreased energy intake is likely due to their distorted self-body image. Based on these findings, we hypothesize that lowering BMI in young women led to increasing prevalence of spina bifida and smaller babies in Japan. This low dietary intake possibly leads to poor folate nutritional status, a risk factor for the development of spina bifida, and increased smoking potentially accelerates these undesirable outcomes. Our hypothesis can be tested using two simultaneous approaches. The first step is an extensive educational campaign for young women to stop smoking, have a realistic body image and eat a sufficient balanced diet. Government officials and health-care workers are encouraged to establish an agenda to educate young women with emphasis on the importance of adequate nutrition during the critical period of reproduction. Together with this campaign, the distribution of folic acid tablets for the prevention of spina bifida can be tried in women of childbearing age through local health centers, which have been well established in Japan.

Birth Weight↗
PubMed1994

Natural interpregnancy intervals of fertile couples: a longitudinal survey of grand grand multiparous women.

OBJECTIVE: To characterize the natural fecundity of grand grand multiparous women (> or = 10 deliveries) in relation to age, number of pregnancies, body mass index, and chronic diseases. DESIGN: A retrospective longitudinal analysis of interpregnancy intervals of married couples who had never used any kind of contraception. PATIENTS, PARTICIPANTS: The interpregnancy intervals (months from delivery or spontaneous abortion to the next conception) of 96 grand grand multiparous women with a total of 1,327 pregnancies were evaluated from the first to the latest pregnancy (14 +/- 1.7; mean +/- SD). Because of the lack of reliable data on conception times, 109 pregnancies had to be excluded. The number of interpregnancy intervals remaining for evaluation was thus 1,218. RESULTS: The mean interpregnancy intervals in the material of 1,218 pregnancies was 8.5 +/- 4.9 months, being significantly shorter after an abortion (5.3 +/- 4.8 months) or stillbirth (6.0 +/- 4.7 months) than after a delivery (8.9 +/- 5.6 months). The interpregnancy interval was significantly longer in women over 30 years of age than in the younger women, approximately 7 months in the latter and exceeding 10 months around the age of 40 years. Body mass index and chronic medical illness did not influence the interpregnancy intervals. The incidence of spontaneous abortions increased after the age of 30 years. It was 6% until 30 years, 10% between 31 and 35 years, and 25% after 40 years. CONCLUSIONS: In this retrospective longitudinal review, the reproductive capacity of fertile couples remains rather sound until premenopausal age. The data suggest that a woman's delivery capacity could be 25 births between 16 and 45 years of age.

Abortion, Induced↗
PubMed2000

Effects of the Zimbabwe Defence Forces training programme on body composition and reproductive hormones in male army recruits.

OBJECTIVES: To investigate the effects of a four month endurance training programme on body composition and reproductive hormone levels. DESIGN: PRE and POST training comparative study. SETTING: Zimbabwe Military Academy, Gweru, Zimbabwe. SUBJECTS: 77 male recruit volunteers participating in the Zimbabwe Defence Forces cadet training programme. MAIN OUTCOME MEASURES: Percent body fat, fat free mass, body mass index, total serum testosterone, luteinising hormone (LH) and follicle stimulating hormone (FSH) compared using the paired t-test. RESULTS: There was a significant decrease in all parameters measured after four months of endurance training. Decreases in body composition parameters were 54% in percent body fat, 6% in fat free mass, and 13% in body mass index. There was a dramatic 58% drop in testosterone, 60% drop in LH and 15% drop in FSH after four months of endurance training. CONCLUSIONS: The Zimbabwe Defence Forces cadet training programme, an endurance training programme induces a state of negative energy balance in trainees. This results in a decrease in % body fat and body mass index due to utilisation of fat stores as a source of energy and a decrease in fat free mass due to gluconeogenic utilisation of muscle protein as energy source for muscle activity. There is impaired hypothalamic-pituitary-testicular axis function as evidenced by the state of hypogonadal-hypogonadism (low testosterone, LH and FSH). This may be attributed to: 1. gonadotrophin releasing hormone pattern generator malfunction due to the stress of intense physical activity and 2. withdrawal of energy expenditure from reproductive machinery as a way of conserving energy for more vital processes in the prevailing state of energy starvation.

Adolescent↗
PubMed1992

The effect of tubal injection of methotrexate on fertility in the rabbit.

OBJECTIVE: To investigate the fertility of rabbits after tubal injection of methotrexate (MTX). DESIGN: The side of injection of MTX was randomly decided in a prospective experimental trial. PARTICIPANTS: Fourteen female New Zealand White Rabbits were believed to be of normal reproductive status. INTERVENTIONS: Methotrexate or Ringer's solution were injected into the tubes of the rabbits. The nidation index was used to measure the fertility of the animals. RESULTS: The average nidation index of the control tubes was not statistically different of the one of the tubes treated with MTX. CONCLUSION: Tubal injection of MTX has no adverse effect on fertility of rabbits. It seems ethical to investigate tubal injection of MTX as an alternative to laparoscopic management of unruptured ectopic pregnancy in the human.

Animals↗
PubMed1988

Weight gain and reproductive function: ultrasonographic and endocrine features in anorexia nervosa.

Pelvic ultrasonographic measurements and reproductive hormone levels in 36 patients with anorexia nervosa were followed as they gained weight during inpatient treatment. In 24 patients who were severely malnourished (69% of premorbid weight) the ovaries were small and amorphous and the levels of LH, FSH and oestradiol were very low. Weight gain led to the appearance of multifollicular ovaries when levels of LH and oestradiol remained low but FSH levels had increased resulting in an LH:FSH ratio of less than 1. The emergence of a dominant follicle in 19 patients after weight gain (to 97% of premorbid weight) was accompanied by an increase in uterine area and associated with increased levels of LH and oestradiol and an LH:FSH ratio greater than 2. Among these patients with a dominant follicle at peak weight, 11 menstruated within a month of discharge. The weight at which normal ovarian morphology returned was related to premorbid weight (P less than 0.002) whereas body mass index (BMI) was poorly related. Our findings suggest that pelvic ultrasonography is probably the best indicator of the weight required for full endocrine recovery and offers advantages over sequential hormonal measurements, and is valuable in the management of patients with anorexia nervosa.

Adolescent↗
PubMed1998

Prolonged inhibition of presynaptic catecholamine synthesis does not alter leptin secretion in normal-weight men and women.

Leptin has been called a hormone of reproduction, and seems to link fat and fertility. It has been speculated that the neurotransmitter norepinephrine (NE) (noradrenaline), possibly via the sympathetic nervous system, may represent the afferent signal which modulates leptin release from adipocytes. The purpose of this study was to produce a state of decreased sympathetic output by using the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine (AMPT), in order to study the effect of this compound on the secretion of leptin from fat cells. Ten subjects (five women and five men) received a total of 5 x 1 g doses of AMPT or 5 x 50 mg promethazine (active placebo) over a 26 h period, separated by 4-6 weeks using a randomized, double-blind, placebo-controlled, cross-over design. Blood samples for hormone measurements were obtained over 24 h (18 time points) on day 2 of each experiment. Urinary measurement of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) on study day 2 served as a marker of the effectiveness of AMPT as an inhibitor of NE synthesis. The daily excretion of this metabolite decreased from 1.56 +/- 0.22 mg in the placebo experiment to 0.53 +/- 0.1 mg in the active experiment (P < 0.05). Plasma leptin concentrations measured in the control group in women and men were similar to those reported previously in lean subjects with a body mass index < 27.5 kg/m2. Leptin concentrations in women were 3-fold higher than in men. Leptin is secreted in a circadian rhythm in both sexes with an increase of nocturnal concentrations by approximately 50%. Two-way analysis of variance reveals no significant difference in leptin secretion between the control and active groups in women and men. In summary, preliminary results do not support the hypothesis that NE represents the afferent signal from the central nervous system which modulates leptin release from adipocytes in the human. Further studies are needed to define the role of the sympathetic nervous system as well as NE in the regulation of leptin secretion and its involvement in obesity and reproduction.

Adult↗
PubMed1995

Preovulatory sonographic uterine receptivity index (SURI): usefulness as an indicator of pregnancy in women undergoing assisted reproductive treatments.

To evaluate the uterine component as a determinant variable in the probability of establishing a pregnancy after assisted reproductive treatments, we introduced a mathematical formula derived from standard endovaginal uterine monitored color Doppler imaging parameters. We analyzed 102 cycles of ovarian stimulation with leuprolide acetate and exogenous gonadotropins resulting in 52 clinical pregnancies by stepwise logistic regression analysis. Sonographic endometrial pattern, thickness, diastolic blood flow, and resistive index variables were transformed into categorical variables and forced to yield a regression equation. Sonographic uterine receptivity index was calculated as a summation of four times endometrial pattern, five times resistive index, and two times diastolic blood flow. This index yielded values for each patient in a range of 0 to 15. Scores > or = 13 were associated with a successful outcome in 79.4% of the patients, whereas scores between 8 and 12 were accompanied by 45.8% pregnancy rates (P = 0.01), and scores < or = 7 had successful treatment outcome in only 7.7% (P = 0.0001). The scores obtained by this mathematical equation provide the ability to make reliable predictions about the outcome of assisted reproductive treatments in women undergoing ovulation induction with leuprolide acetate and human menopausal gonadotropins.

Adult↗
PubMed2003

The burden of anemia among women in India.

OBJECTIVE: This research investigates the prevalence and determinants of anemia among women in Andhra Pradesh. We examined differences in anemia related to social class, urban/rural location and nutrition status body mass index (BMI). We hypothesized that rural women would have higher prevalence of anemia compared to urban women, particularly among the lower income groups, and that women with low body mass index (BMI; <18.5 kg/m(2)) would have a higher risk compared to normal or overweight women. DESIGN: The National Family Health Survey 1998/99 (NFHS-2) provides nationally representative cross-sectional survey data on women's hemoglobin status, body weight, diet, social, demographic and other household and individual level factors. Ordered logit regression analyses were applied to identify socio-economic, regional and demographic determinants of anemia. SETTING: Andhra Pradesh, a southern Indian state. SUBJECTS: A total of 4032 ever-married women aged 15-49 from 3872 households. RESULTS: Prevalence of anemia was high among all women. In all 32.4% of women had mild (100-109.99 g/l for pregnant women, 100-119.99 for non-pregnant women), 14.19% had moderate (70-99.99 g/l), and 2.2% had severe anemia (<70 g/l). Protective factors include Muslim religion, reported consumption of alcohol or pulses, and high socioeconomic status, particularly in urban areas. Poor urban women had the highest rates and odds of being anemic. Fifty-two percent of thin, 50% of normal BMI, and 41% of overweight women were anemic. CONCLUSIONS: New program strategies are needed, particularly those that improve the overall nutrition status of women of reproductive ages. This will require tailored programs across socio-economic groups and within both rural and urban areas, but particularly among the urban and rural poor.

Adolescent↗
PubMed1999

Menstrual history and bone density in young women.

Adequate levels of reproductive and pituitary hormones are needed for the initiation and maintenance of regular menstrual cycles as well as for the achievement of peak bone mineral density (BMD). Therefore, in the absence of direct hormone measures, menstrual history may serve as a surrogate for the adequacy of hormonal functioning and be a marker for bone status in young women. In our cross-sectional study of white college women aged 19-26 years, we examined the association of six characteristics of menstrual history with bone density at the lumbar spine and the femoral neck. To characterize associations, we used multiple linear regression models that also accounted for the contribution of body mass index, dietary calcium intake, height, level of physical activity, smoking, and alcohol use. The associations between each of the six menstrual characteristics and BMD were stronger at the lumbar spine than at the femoral neck. Age at menarche explained the most variance at both the lumbar spine (partial r2 x 100 = 5.9%) and the femoral neck (partial r2 x 100 = 2.1%). For each year that menarche was delayed, bone density was lower by -0.023 g/cm2 (p = 0.0024) at the lumbar spine and -0.0129 g/cm2 (p = 0.0565) at the femoral neck. At the lumbar spine, a higher number of lifetime menstrual cycles was also significantly associated with increased bone density (adjusted beta = 0.0010, p = 0.0052, partial r2 x 100 = 4.4%). This association was not significant after adjusting for age at menarche. Neither reproductive years (age - age at menarche) nor a history of irregular cycles (either at menarche, in the past year, or ever) was associated with bone density at either site. Menstrual function appears to affect the bone density of these young women. Studies that include measures of reproductive and pituitary hormones are needed to further explore the role of hormones in the potential link between menstrual history and bone density.

Absorptiometry, Photon↗
PubMed1999

Clinical aspects, outcome assessment, disease course, and extra-articular features of spondyloarthropathies.

Much has been written over the years regarding the clinical aspects and disease course of the spondyloarthropathies, but publications relating to outcome assessment that attempt to relate measures of process with outcome are few. Extra-articular features of the spondyloarthropathies, eg, uveitis, colitis, and aortitis, are well described, but in the past few years there has been an increasing interest in the incidence of osteoporosis in this group of patients, particularly those with ankylosing spondylitis. In rheumatoid arthritis functional indices have been developed, such as the Health Assessment Questionnaire score, which has been shown to be robust in monitoring response to therapy, but the situation is quite different in a condition such as ankylosing spondylitis. In the last few years a number of functional indices have been developed that are now beginning to be applied to monitor response to treatment in the spondyloarthropathies. The impact of ankylosing spondylitis in women is an area that has been neglected in the past, and a recent review addresses the effects of the disease on the reproductive capacity in women. This overall review of the past year's publications from the clinical aspects of ankylosing spondylitis confirms that clinical research still has much to contribute to this fascinating group of disorders.

Aortitis↗
PubMed1997

Quantitative analysis of constitutive heterochromatin in couples with fetal wastage.

PROBLEM: Heteromorphism of constitutive heterochromatin is a stable evolutionary feature that is thought to cause no phenotypic alterations. Nevertheless, the role of constitutive heterochromatin is still unknown. The instability of constitutive heterochromatin was generally restricted to T-lymphocytes and was associated with variable immunodeficiency. The heterochromatin regions of chromosomes 1, 9, 16, and Y have been postulated to play a role in the immune response and during early embryo development. METHOD OF STUDY: To investigate a possible influence of constitutive heterochromatin in human reproductive ability, quantitative analysis of constitutive heterochromatin in human chromosomes 1, 9, 16 and Y was done. Thirty couples were divided into two groups, owing to the clinical heterogeneity of their reproductive disorders. The first group included couples with two or more spontaneous abortions as the only pregnancy outcomes, and the second group included couples with a stillborn child with or without malformations. In the control group were couples with one or more healthy children without a history of fetal wastage. All of the persons in this study had normal karyotypes. The amount of constitutive heterochromatin was expressed by relative value using the simple transformation [q/(p + q)]. This value, obtained on GTG-banded metaphase chromosomes, represented an indirect measure of heterochromatin content. The Y/F index was used to express the relative amount of heterochromatin in chromosome Y. RESULTS: There was a significant increase in the heterochromatin content of the chromosomes 16 homologue pair in males and females with a stillborn or a stillborn malformed child (P < 0.01) and an increase in total heterochromatin cell content compared to controls (P = 0.005). The same couples had significantly increased mean maximal heterochromatin content in the potential zygotes (P < 0.02). The couples who experienced spontaneous abortions only had a minimal total heterochromatin content in the potential zygotes (P < 0.05). The Y/F index was significantly lower in the males in both groups compared to controls (P1 < 0.02; P2 < 0.02). CONCLUSION: The quantitative analysis of constitutive heterochromatin could be valuable in predicting pregnancy outcome.

Abortion, Spontaneous↗
PubMed2006

Predictive factors and a corresponding treatment algorithm for controlled ovarian stimulation in patients treated with recombinant human follicle stimulating hormone (follitropin alfa) during assisted reproduction technology (ART) procedures. An analysis of 1378 patients.

BACKGROUND: Identifying parameters that can accurately predict the response to controlled ovarian stimulation (COS) would be of great benefit in assisted reproductive technology (ART) procedures. An analysis was undertaken with the objective of determining whether specific factors could optimally predict a response to stimulation in ART, and to then develop a corresponding treatment algorithm that could be used to calculate the optimal starting dose of recombinant human follicle stimulating hormone (r-hFSH; follitropin alfa) for selected patients. METHODS: The overall population consisted of 2280 normo-ovulatory ART patients from 11 randomised clinical trials. However, for the final analysis population, only patients less than 35 years of age who received r-hFSH monotherapy (N = 1378) were included. RESULTS: Backwards stepwise regression modelling indicated that predictive factors for ovarian response included basal FSH, BMI, age and number of follicles < 11 mm at baseline screening. The concordance probability index was 59.5% for this model. CONCLUSIONS: In the largest data series so far analysed to determine predictive factors of ovarian response, basal FSH, BMI, age and number of follicles < 11 mm at screening were the most important variables in ART patients less than 35 years of age who were treated with r-hFSH monotherapy. Using these four predictive factors, a follitropin alfa starting dose calculator was developed that can be used to select the FSH starting dose required for an optimal response. The relevance of this dose calculator will be evaluated in a prospective clinical trial.

Adolescent↗