Joop Schoemaker

Intrauterine insemination or in-vitro fertilisation in idiopathic subfertility and male subfertility: a randomised trial and cost­ effectiveness analysis

BACKGROUND Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis. METHODS In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis. FINDINGS 86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12.2% vs 7.4% and 8.7%, respectively; p=0.09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 [42%] drop-outs vs 13 [15%] and 14 [16%], respectively; p<0.01). The womans age was the only factor that influenced a couples chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423-10661 Dutch guilders [US

Polycystic ovaries in adolescents and the relationship with menstrual cycle patterns, luteinizing hormone, androgens, and insulin

4511-5710] for IUI vs 27409 Dutch guilders [US

LUTEINIZING HORMONE AND FOLLICLE STIMULATING HORMONE SECRETION PATTERNS IN BOYS THROUGHOUT PUBERTY MEASURED USING HIGHLY SENSITIVE IMMUNORADIOMETRIC ASSAYS

14679] for IVF). INTERPRETATION Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment.

Higher risk of preeclampsia in the polycystic ovary syndrome: A case control study

STUDY OBJECTIVE To evaluate the possible role of inappropriate LH secretion, hyperandrogenism, and hyperinsulinemia in the development of polycystic ovaries (PCO) and the polycystic ovary syndrome. DESIGN Observational. SETTING General population samples. PARTICIPANTS 58 adolescents with regular menstrual cycles, 50 with irregular menstrual cycles, and 29 with oligomenorrhea (age 16.7+/-0.9 years). INTERVENTIONS Transabdominal pelvic ultrasonography and vena puncture. MAIN OUTCOME MEASURES PCO; LH, androstenedione, and testosterone levels; overnight fasting insulin concentrations; and oligomenorrhea. RESULTS The prevalence of PCO increased significantly with the irregularity of the menstrual cycle pattern, as illustrated by the study, finding PCO in 9% of the girls with regular menstrual cycles, 28% of those with irregular menstrual cycles, and 45% of oligomenorrheic girls. The LH and androgen concentrations were significantly higher in girls with PCO; the insulin levels and the glucose-insulin ratio did not differ when the girls with PCO were compared with girls with normal ovaries. Oligomenorrheic girls with PCO had the highest androgen and LH concentrations; their insulin concentrations and glucose-insulin ratio were in the same range as girls with regular menstrual cycles and normal ovaries; and both their hip and waist girths were wider, although their waist-hip ratio was normal. CONCLUSIONS PCO in adolescents is associated with irregular menstrual cycles, oligomenorrhea, and/or high androgen and LH levels; but no relationship was found with the insulin level or glucose-insulin ratio. Thus, it is doubtful that hyperinsulinemia is an important factor in the development of PCO or polycystic ovary syndrome.

Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study *

Pulsatile gonadotrophin secretion patterns were studied in 36 healthy girls by measuring every 10 min and applying immunoradiometric assays (IRMA). Different stages of puberty were associated with significant changes in the plasma LH and FSH levels, pulse numbers (Pno) and pulse amplitudes (pA). Plasma LH was not detectable by day or night in young prepubertal girls (B 1), neither was plasma oestradiol (E2); however, plasma FSH was detectable in a pulsatile pattern. In the older prepubertal girls (B1‐onset) a discrete pulsatile LH pattern became detectable only during the night; plasma FSH tended to rise, while E2 became just detectable. In the early pubertal girls (B2) most daytime LH values were above the detection limit, in some with low‐amplitude pulses. At night, pulses with a wide range of pulse amplitudes were detected. Plasma FSH increased further, plasma E2 only slightly. With the progression of puberty the plasma LH and FSH levels, Pno and pA increased significantly from stage B2 to B3 during the day (P |Ml 0.05) and close to significance during the night (0‐05 |Ml P |Ml 0.1). However, in stage B4 the secretory characteristics tended to decline, while from stage B3 onwards plasma E2 started to rise rapidly (P 0.05, during the night from stage B2 to B3, during the day from B3 to B4m —). Simultaneous LH and FSH pulses were observed throughout puberty, usually during the night. Using these IRMA methods nocturnal LH in older prepubertal girls and both diurnal and nocturnal FSH pulsatility could be demonstrated in young prepubertal girls. From this study we conclude that (1) puberty in girls, as in boys, may be brought about by an increasing GnRH secretion both in frequency and amplitude, first appearing during the night. This increased GnRH stimulation results in LH secretion only during the night; (2) a cyclical pulsatile LH pattern including an LH surge can be established before the menarche; the capacity for positive feedback activity is not the final maturation characteristic to achieve an ovulatory menstrual cycle.

Apoptotic cell death in human granulosa-lutein cells: a possible indicator of in vitro fertilization outcome

OBJECTIVE To determine whether the risk of pregnancy-induced hypertensive disorders (PIHD) is higher in patients with the polycystic ovary syndrome (PCOS) than in non-PCOS controls, matched for age and parity. STUDY DESIGN Retrospective analysis of eighty-one patients with PCOS, consecutively becoming pregnant during a seven-year period. Each PCOS-patient was matched for age and parity with one control patient. Chi-squared, Mann-Whitney or Fishers exact-tests were used for statistical analysis. RESULTS Overall incidence of PIHD was similar in both study groups. However, incidence of preeclampsia was significantly higher in patients with PCOS than in controls (P = 0.02). This higher incidence can not be explained by body mass index, endocrine profile before pregnancy, induction of ovulation or treatment regimens. CONCLUSIONS PCOS-patients are at a significantly higher risk for preeclampsia than non-PCOS controls.

Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles

In the present prospective study we compared, in terms of pregnancy rates, the differences between intrauterine insemination (IUI) of in vitro capacitated husbands semen and timed natural intercourse in spontaneous or clomiphene citrate (CC) stimulated cycles. A rapid urinary luteinizing hormone peak detection test was used for timing of ovulation. Forty patients suffering from longstanding infertility of male (n = 17), cervical (n = 2), and idiopathic (n = 21) origin were randomly assigned into four distinct treatment modalities during 4 consecutive cycles. A total of 132 cycles were analyzed. In 35 cycles treated with CC plus IUI, five conceptions were achieved, whereas three pregnancies occurred in 32 inseminated spontaneous cycles. Only 1 patient conceived after timed intercourse in 31 CC stimulated cycles, and no pregnancy resulted from 34 spontaneous cycles combined with timed intercourse. There was a statistically significant higher conception rate in cycles in which IUI was performed, whereas the use of CC does not seem to improve the pregnancy rate. Analysis of results for other modifying factors did not substantially affect the relative risk (odds ratio) of pregnancy.

Analysis of peripheral blood lymphocyte subsets, NK cells, and delayed type hypersensitivity skin test in patients with premature ovarian failure.

OBJECTIVE To determine whether women who do not conceive during an IVF treatment despite normal FSH levels have a higher rate of apoptosis in their granulosa-lutein cells than women who do conceive. DESIGN Prospective. SETTING Large teaching hospital and fertility center. PATIENT(S) Patients with normal FSH levels undergoing an IVF treatment. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Outcome of the IVF treatment and percentage of apoptotic granulosa-lutein cells. RESULT(S) A significantly lower percentage of granulosa-lutein cells were apoptotic in patients who became pregnant compared with those who did not become pregnant. A higher basal FSH level was significantly correlated with the duration of the stimulation, and the number of follicles was significantly inversely correlated with the number of ampules of FSH used and the duration of the treatment. The number of embryos was significantly correlated with the number of oocytes, and significantly inversely correlated with the number of apoptotic granulosa-lutein cells. CONCLUSION(S) Fewer granulosa-lutein cells are apoptotic in women who have an ongoing pregnancy after IVF treatment than in women who do not conceive.

Pregnancy rates after timed intercourse or intrauterine insemination after human menopausal gonadotropin stimulation of normal ovulatory cycles: a controlled study *

OBJECTIVE To examine whether follicle loss due to ovarian aging is responsible for the occurrence of regular menstrual cycles in aging women with polycystic ovary syndrome (PCOS), the size of the FSH-sensitive follicle cohort was estimated by the exogenous follicle-stimulating hormone ovarian reserve test (EFORT) and related to the follicle count as measured by ultrasound. DESIGN Prospective study. SETTING Reproductive endocrinology unit of an academic medical center. PATIENT(S) Twenty-seven aging women with PCOS (35.8-49.4 years): 20 with regular menstrual cycles and 7 with oligomenorrhea or amenorrhea. INTERVENTION(S) EFORT and transvaginal ultrasound. MAIN OUTCOME MEASURE(S) Baseline (cycle day 2, 3, or 4) FSH, androstenedione (A), T, E(2), and inhibin B levels, the E(2) and inhibin B increment after the EFORT, and the follicle count. RESULT(S) After correction for the body mass index (BMI), the inhibin B increment was higher in the irregular menstrual group, but the E(2) increment did not differ significantly between the two groups. Ultrasound showed a median follicle count of 8.5 (4.0-18.0) in women with regular menstrual cycles (n = 16), compared with 18.0 (8.0-35.0) in irregularly menstruating women (n = 7). The follicle count was significantly correlated to the FSH-induced E(2) increment (r = 0.656) as well as to the inhibin B increment (r = 0.654). The regularly menstruating group was significantly older, had a higher basal FSH concentration, and had lower androgens than the irregularly menstruating group. CONCLUSION(S) The smaller follicle count, the older age, the higher FSH concentration, and the lower FSH-induced inhibin B increment found in women with PCOS and a regular menstrual cycle confirm that a decrease in the size of the follicle cohort due to ovarian aging is largely responsible for the regular menstrual cycles in aging PCOS women.

Obesity, rather than menstrual cycle pattern or follicle cohort size, determines hyperinsulinaemia, dyslipidaemia and hypertension in ageing women with polycystic ovary syndrome.

PROBLEM: Premature ovarian failure (POF) probably belongs to the group of autoimmune endocrinopathies. Cell‐mediated immune parameters were investigated. Sex steroids have a profound effect on the immune system. POF patients and postmenopausal control women (PM) were tested with or without estrogen substitution.