LH Values Research Articles

Device Design of High–Speed Source–Heterojunction–MOS Transistors (SHOTs): Optimization of Source Band Offset and Graded Heterojunction

We have studied the device design of 15-nm highspeed n-channel source-heterojunction-MOS transistors (SHOTs) utilizing high-velocity electron injection from the source into the channel region and using the conduction-band-offset energy between the source and the channel regions. The band-offset energy near the source region and the length of the graded heterojunction are key parameters for realizing high-speed operation of SHOTs. A 2D device simulator indicates that the enhancement in transconductance Gm in SHOTs on an SOI substrate over conventional SOI-MOSFETs without source-heterojunction structures strongly depends on the source conduction-band-offset value DeltaEc and the length of graded-heterojunction structures LH in SHOTs. Moreover, the Gm enhancement of SHOTs is affected by the drain and the gate biases. We have shown that, with fully optimized DeltaEc and LH values, the Gm enhancement of SHOT due to high-velocity electron injection can be achieved in a whole range of drain bias. The optimized SHOT is quite promising for high-speed CMOS devices in the 10-nm regime.

Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4´-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD draft protocols

We performed an uterotrophic assay, the Hershberger assay, and a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) of 4,4 -[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] based on the OECD draft protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and the uterine weight of rats given the 1,000 mg/kg dose of the test chemical plus ethinyl estradiol decreased. In the Hershberger assay, the test chemical was orally administered at doses of 0, 100, 300, and 1,000 mg/kg day to castrated male SD rats for ten consecutive days beginning on postnatal day 56, and no changes were observed. On the other hand, when the test chemical was orally administered at doses 0, 100, 300, and 1,000 mg/kg day for at least 28 days, a decrease in LH values in rats of both sexes and a decrease in FSH and estradiol values in female rats were detected in the 1,000 mg/kg group, and abnormal estrous cycles, uterine glandular atrophy, persistence of ovarian corpora lutea, vaginal epithelial mucification, and mammary glandular hyperplasia were also observed in one female rat in the 1,000 mg/kg group. Therefore, the uterotrophic assay used in this study showed that the chemical has the estrogen-antagonist properties, and some potentially endocrine-mediated effects were detected in growing rats based on the results of the enhanced OECD test guideline No. 407. However, the changes were observed in rats given a high dose of the chemical, 1,000 mg/kg day.

LH response of seasonally anovular Corriedale ewes acutely exposed to rams and estrous ewes

Serial blood sampling before and after exposing four anovular Corriedale ewes to a group of rams and estrous ewes during the non-breeding season revealed a pattern of LH secretion similar to that previously observed in Merinos. Mean LH values doubled ( P < 0.001) from 0.24 ± 0.06 μg L −1 (mean ± s.e.m.) before to 0.55 ± 0.05 μg L −1 after 2 h of visual, auditory, and odor exposure to rams and estrous ewes in an indoor facility. A non-significant ( P < 0.17) increase of LH pulses per hour was also observed (0.7 ± 0.3 pulses per hour before compared with 1.3 ± 0.3 during stimulation). All four ewes had recently formed corpora lutea by five days after stimulation. Results are consistent with the pattern of sudden increase and sustained release of LH observed in other sheep breeds, particularly the Merino.

Recombinant-follicle stimulating hormone is more effective than urinary human menopausal gonadotropin in ovarian hyperstimulation for assisted reproductive technology treatment.

Aim: The aim of the present study was to establish a standard protocol for ovarian stimulation with gonadotropin-releasing hormone analog (GnRH-a) long protocol using recombinant-follicle stimulating hormone (rec-FSH) preparations for assisted reproductive technology (ART) treatment. Methods: In 86 patients who underwent ovarian stimulation with GnRH-a long protocol for ART treatment, 53 were stimulated by rec-FSH preparations (rec-FSH group) and the others were stimulated by urinary-hMG (u-hMG group) preparations. The subjects were randomly assigned to either of these preparations. Hormonal profiles, total doses of gonadotropins, duration of stimulation and ART results were compared in both groups. Results: The duration of stimulation was similar in both groups (9.2±0.3days and 9.2±0.2days, respectively). The total doses of gonadotropin in the rec-FSH group (1505.3± 29.2IU) was significantly lower than those in the u-hMG group (2130.3±54.6IU, P<0.0001). The FSH and LH values on the day of human chorionic gonadotropin (hCG) administration in the rec-FSH group were significantly lower than those in the u-hMG group. Pregnancy rates were 31.3% in the rec-FSH group and 33.3% in the u-hMG group, respectively. Conclusions: The present study showed that rec-FSH preparations were more potent than conventional u-hMG preparations and the protocol of the present study with rec-FSH was a new ovarian stimulation protocol with GnRH-a long protocol. (Reprod Med Biol 2007; 6: 27-32).

Assessment of Basal and Gonadotropin-Releasing Hormone-Stimulated Gonadotropins by Immunochemiluminometric and Immunofluorometric Assays in Normal Children

Recently, new methodologies have been applied to commercial immunofluorometric (IFMA) and immunochemiluminometric (ICMA) LH and FSH assays. The objective of the study was to use ICMA to establish basal and GnRH-stimulated LH and FSH reference values in normal subjects of different ages and sexual development, compared with IFMA. We established basal and GnRH-stimulated LH and FSH levels of 315 prepubertal and pubertal children (170 males and 145 females) divided into five groups according to Tanner stage. Of these, 106 subjects (59 males and 47 females) were submitted to GnRH test. The prepubertal upper limit of normal for basal LH, determined by the 95th percentiles of the prepubertal population, were 0.2 IU/liter (ICMA) and 0.6 IU/liter (IFMA) in both genders. No overlap of basal LH levels determined by ICMA was observed between prepubertal and pubertal males, but basal LH determined by IFMA overlapped in 11.8% of subjects. In girls, both methods yielded overlapping values (10.4%, ICMA; and 84.6%, IFMA). The LH peak after GnRH stimulation that defined puberty was 4.1 IU/liter (ICMA) and 3.3 IU/liter (IFMA) in boys and 3.3 IU/liter (ICMA) and 4.2 IU/liter (IFMA) in girls. After GnRH stimulation, values determined by the two methods overlapped in both genders. We conclude that ICMA is more sensitive and precise than IFMA, permitting differentiation of pubertal and prepubertal stage in boys under basal conditions. However, in girls the overlap of basal values was marked, indicating the need for the GnRH test to establish maturity of the hypothalamus-pituitary-gonadal axis.

Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept

We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.

Precocious Puberty in a Girl with Floating-Harbor Syndrome

Floating-Harbor syndrome (FHS) is a rare genetic disorder characterized by short stature, delayed bone age, mild to moderate mental retardation, speech problems, and peculiar craniofacial features. In these patients pubertal development has been reported to be normal. In this paper, we describe a girl with FHS who developed precocious puberty. FHS diagnosis was made at 2 years 5 months on the basis of peculiar clinical features. At 7 years 7 months, the girl began pubertal development; her height was 112.5 cm (-2.42 SDS) and pubertal staging was B2 PH2 AH1. LHRH test underlined LH and FSH peak values of 11.7 mIU/ml and 6.2 mIU/ml, respectively. Plasma levels of 17beta-estradiol were normal (8.5 pg/ml). Ophthalmological and neurological examinations, including nuclear magnetic resonance imaging of the brain, were normal. Treatment with gonadotrophin-releasing hormone analogue was begun. At 10 years 1 month, because of reduced height velocity, her growth hormone secretion was evaluated with diagnosis of neurosecretory dysfunction; hGH therapy was begun. The patient showed a good response to hGH treatment, reaching a normal adult height (156.1 cm; -1.20 SDS). This report suggests that, in patients with FHS, precocious puberty should be taken into consideration; in these patients, a careful endocrinological followup for the possible presence of growth and pubertal disorders is needed.

MENSTRUAL CYCLE IN WOMEN ADDICTED TO ALCOHOL DURING THE FIRST WEEK FOLLOWING DRINKING CESSATION--CHANGES OF SEX HORMONES LEVELS IN RELATION TO SELECTED CLINICAL FEATURES

To assess the prevalence of hormonal dysfunction in women addicted to alcohol during first week following drinking cessation; to determine whether fluctuations of hormone levels in follicular, ovulation and luteal phases in addicted women are equal to those normally found in healthy women; to determine the association between hormonal imbalances with selected clinical features. Biochemical parameters of liver function and hormone levels were assessed in 30 women treated for 30 days in a Short Term Therapy and Detoxification Ward. The following hormones were measured: prolactin (PROL), folliculotropin (FSH), luteotropin (LH), estradiol (ES) and testosterone (TEST)--(i) after menstruation, at follicular phase, between 5th and 7th day of the cycle; (ii) around ovulation, 11-14th day of the cycle; and (iii) before menstruation, at luteal phase, between 19th and 22th day of the cycle. Mean PROL levels in all three cycle phases and progesterone level in follicular phase were above, while mean TEST level was below, the reference values. Over 50% of women had abnormally increased PROL values in all phases of the cycle while decreased values of PROG or LH were found in approximately 50% and >30% of study women. The menstrual cycle disturbances in alcoholic women are most prominent around the middle part of the cycle and age influences the pattern of hormonal changes.

GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy rates in IUI-stimulated cycles. A prospective randomized trial

Our prospective randomized controlled trial was designed to assess whether the use of GnRH antagonists can improve the success rate of controlled ovarian stimulation (COS)/intrauterine insemination (IUI) treatments, via inhibition of the premature LH rise. A total of 104 patients were randomly divided, using a randomization list, into two groups: in group A (n = 52), recombinant FSH (rFSH) was given with GnRH antagonist Cetrorelix, and in group B (n = 52), the patients received rFSH alone in a manner similar to that of group A. The primary outcome measure was clinical pregnancy rate per couple. The pregnancy rate per patient was 53.8% in group A and 30.8% in group B (P = 0.017). The rate of premature LH surge was 7% in group A and 35% in group B (P < 0.0001). A premature luteinization was observed in two cycles of 144 in group A (1.4%) and in 16 cycles of 154 in group B (10.4%) (P = 0.001). The mean values of LH and progesterone were significantly lower in patients receiving GnRH antagonist than in those who did not (3.3 +/- 3.3 mIU/ml in group A versus 9.9 +/- 7.9 mIU/ml in group B, P < 0.0001, for LH; 1.3 +/- 1.1 ng/ml versus 2.1 +/- 1.9 ng/ml for group A and B, respectively, P < 0.0001, for progesterone). The use of GnRH antagonist in COS/IUI cycles improves pregnancy rate, preventing the premature LH rise and luteinization.

Obesity and Male Reproductive Potential

Obesity and Male Reproductive Potential

Influence of pituitary suppression with triphasic or monophasic oral contraceptives on the outcome of in vitro fertilization and embryo transfer

To compare the clinical outcome of IVF treatment after pituitary suppression with two different oral contraceptives (OCs). 65 patients who received IVF treatment was classified into 2 groups based on the difference of OCs they used for pituitary suppression before ovarian hyperstimulation. Group 1 included 36 patients who received monophasic OCs. Group 2 included 29 patients who received triphastic OCs. Both groups received the OCs from the 5th day of the cycle for consecutive 21 days. The hormone profiles after OCs and clinical outcome of IVF treatment were compared between two groups. Two-sample t-tests and X2 tests were used for statistical analyses. P < 0.05 was considered statistically significant. The mean age and basal hormone profiles were comparable between two groups. After ovulation suppression with different OCs, the day 2 FSH and LH value revealed statistically significant difference between two groups(4.2+/-1.8 vs 6.0+/-2.6; 2.7+/-2.0 vs 4.2+/-3.3 respectively). The numbers of oocyte per retrieval and fertilization rate were comparable between two groups, but higher quality embryos as revealed by the cleavage speed were noted in the triphastic OCs group. Although statistically not significant, higher implantation rate and pregnancy rate were also noted in the triphastic OCs group. Different OCs for pituitary suppression can result in different hormone profiles. Ovulation induction in IVF treatment should be individualized according to these hormone changes to achieve the optimal clinical outcome. Triphastic OCs exceeds monophastic OCs in producing good quality embryo in IVF-ET treatment.

Unusual presentation of juvenile granulosa cell tumor of the ovary

We present a case report of juvenile granulosa cell tumor of the ovary (JGCT) with an unusual clinical presentation and hormonal secretion. A 16-yr-old girl had developed spontaneous menarche at the age of 12 yr, but after this initial menstrual bleeding she had no further periods for 4 yr. She had no clinical signs of virilization. Endocrinological studies detected high levels of DHEA, 17 hydroxyprogesterone (17OH-P), insulin and PRL, an exaggerated DHEA response after ACTH stimulation, and low FSH and high LH values after GnRH. An ultrasound examination revealed an irregular structure and increased diameters of her right ovary, due to the presence of a cyst. Because exploratory laparoscopy revealed the presence of a right ovarian mass, her right ovary was removed. JGCT was diagnosed. Ten days after surgery, menstrual bleeding initiated. Endocrinological evaluation after the operation showed that 17OH-P, insulin and basal FSH and LH serum values had returned to normal, while DHEA levels had decreased to within the upper limit of the normal range. Only PRL levels remained unchanged. Our patient presented some unusual characteristics. She did not have precocious puberty, but secondary amenorrhea. Hormonal secretion consisted mainly of androgens, even though clinical signs of virilization were not present.

Gonadotropin dysfunction in women with polycystic ovary syndrome

Gonadotropin abnormalities are common in women with polycystic ovary syndrome. Interpretation of LH values depends on body weight, time of last ovulation, assay used, and the precision of the normative data against which a value is compared.

Comparison and Problems of Measured Values of LH, FSH, and PRL among Measurement Systems

Several measurement systems are used for LH, FSH, and PRL in Japan, but the comparison of the measured values is difficult in some cases. In this study, we compared the measured values of 3 types of measurement systems widely used in Japan, SPAC-S, ARCHITECT, and Centaur, in females with a normal menstrual cycle and with various ovulatory disorders. Variant LH was discriminated by the criterion, SPAC-S LH/ARCHITECT LH ratio <0.5. Excluding the variant LH, the correlation of the measured LH values among the measurement systems was high, 0.94-0.99, and the value measured by ARCHITECT LH and Centaur LH was slightly higher than that measured by SPAC-S LH. As for FSH, the correlation was also high, 0.94-1.00, and the value measured by ARCHITECT FSH and Centaur FSH was slightly lower than that measured by SPAC-S FSH. The important judgment criterion of polycystic ovary syndrome (PCOS), a high level of LH relative to FSH, has been set to 1.0 or higher LH/FSH using SPAC-S. When the regression line of the LH/FSH ratio among the measurement systems was investigated, it can be said that 1.25 or higher by ARCHITECT and 1.40 or higher by Centaur are appropriate for the judgment criteria of a high level of LH relative to FSH. As for PRL, the correlation was high, 0.96-0.99, but the value showed large differences among the systems. For the diagnosis of hyperprolactinemia, the higher limit of the normal range may be 15 ng/mL for SPAC-S, 30 ng/mL for ARCHITECT, and 24 ng/mL for Centaur.

Treatment with the GnRH antagonist ganirelix prevents premature LH rises and luteinization in stimulated intrauterine insemination: results of a double-blind, placebo-controlled, multicentre trial*

This study was designed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization (LH+progesterone rises). Women of infertile couples, diagnosed with unexplained or male factor infertility, were randomized to receive either ganirelix (n=103) or placebo (n=100) in a double-blind design. All women were treated with an individualized, low-dose rFSH regimen started on day 2-3 of cycle. Ganirelix (0.25 mg/day) was started if one or more follicles>or=14 mm were visualized. Ovulation was triggered by HCG injection when at least one follicle>or=18 mm was observed and a single IUI was performed 34-42 h later. The primary efficacy outcome was the incidence of premature LH rises (+/-progesterone rise). In the ganirelix group, four subjects had a premature LH rise (value>or=10 IU/l), one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment, whereas in the placebo group 28 subjects had a premature LH rise, six subjects prior to the start of placebo and 22 subjects during placebo treatment. The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles (3.9 versus 28.0%; P=0.003 for ITT analysis). When excluding subjects with an LH value>or=10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles (2.9 versus 23.4%; P=0.003 for ITT analysis). Premature luteinization (LH rise with concomitant progesterone rise>or=1 ng/ml) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation. Ongoing pregnancy rates per attempt were 12.6 and 12.0% for the ganirelix and placebo groups respectively. Treatment with ganirelix effectively prevents premature LH rises, luteinization in subjects undergoing stimulated IUI. Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working.

Evidence That Termination of the Estradiol-Induced Luteinizing Hormone Surge in Women Is Regulated by Ovarian Factors

The endogenous LH surge is the result of the estrogen-positive feedback effect. However, the factors that are responsible for the termination of LH surge are not known. The objective of the study was to investigate the mechanism that terminates the LH surge in women. Eight normally cycling women (aged 42-48 yr) were investigated in two cycles, i.e. cycle 1 (control) and cycle 2. In cycle 2 total abdominal hysterectomy plus bilateral salpingooophorectomy was performed on d 3. In both cycles, estradiol was administered transdermally at the dose of 100 microg on d 3 and 150 microg on d 4 and 5. Blood samples were obtained every 12 h from d 3 to 5 and every 6 h thereafter until d 9. In both cycles, after suppression of gonadotropins, the women displayed an endogenous LH surge. The time intervals between the commencement of estradiol treatment and the LH surge onset (73.5 +/- 1.5 vs. 76.5 +/- 2.5 h) and peak LH values (11.4 +/- 1.9 vs. 12.4 +/- 3.1 IU/liter) were comparable in the two cycles (mean +/- sem). After peaking, LH values decreased gradually in cycle 1, whereas in cycle 2 they remained stable and were higher than the corresponding values in cycle 1 (P < 0.05). Before the LH surge onset, estradiol values showed in both cycles a preovulatory pattern of changes, but starting 24 h after the onset of the LH surge, they were lower in cycle 2 (P < 0.05). Progesterone levels were similar in both cycles until the day of the LH surge onset, but in cycle 2 they declined thereafter and were lower than in cycle 1 (P < 0.05). It is suggested that ovarian factors rather than exhaustion of pituitary reserves are important for termination of the endogenous LH surge during the normal menstrual cycle.

D-Aspartate and reproductive activity in sheep

d-Aspartic acid ( d-Asp) has been isolated from neuroendocrine tissues of many invertebrates and vertebrates. Recently, it has been demonstrated that this d-amino acid may be converted to N-methyl- d-aspartic acid (NMDA), a neuromodulator associated with sexual activity. In this study, we determined d-Asp and NMDA concentrations in endocrine glands and other tissues in ewes after d-Asp administration and in controls. We also evaluated the effects of d-Asp administration on the reproductive activity of ewes by determining either progesterone concentrations or LH pulses in the presence or absence of estradiol benzoate. The pineal gland showed the highest natural content of d-Asp (1.47 ± 0.22 μmol/g tissue), whereas the pituitary gland had the highest capability to store d-Asp, with a peak value (9.7 ± 0.81 μmol/g tissue) 6 h after its administration. NMDA increased sharply 12 h following d-Asp administration, reaching values three times higher than the baseline in both the pituitary and brain. d-Asp was quickly adsorbed after subcutaneous administration, with a peak in plasma levels 2 h after administration and a return to baseline values after 6 h. d-Asp administration achieved a significant ( P < 0.001) increase in LH values with respect to estradiol or estradiol + d-Asp treatments. d-Asp treatment once or twice a week did not successfully drive acyclic ewes into reproductive activity. In conclusion, the results obtained in this study demonstrated that d-Asp is endogenously present in sheep tissues and electively stored in endocrine glands and brain after its administration. NMDA and LH increase following d-Asp administration suggesting a role of this d-amino acid in the reproductive activity of sheep.

Influence of estradiol on adrenal activity in ovariectomized cows during acute stress

Stress-dependent activation of the hypothalamo-pituitary-adrenal axis (HPA) can compromise reproductive function in animals and humans. In addition, it has been shown that estrogens are also capable of influencing the activity of the adrenal cortex. The objective of this study was to evaluate the effect of estradiol (E2) on adrenocortical secretion of cortisol and progesterone as well as on pituitary LH-release in cows during stress. Five ovariectomized Brown Swiss cows were exposed to acute restraint stress (2-h immobilization in a trimming chute), either with or without E2 treatment. Blood samples were taken every 15 min during a 5-h period for determination of cortisol progesterone and LH. Our results demonstrate that during the 2-h stress period mean cortisol concentrations significantly ( P < 0.05) increased in all cows independent of E2 treatment. Mean progesterone concentrations also increased during stress, but the effect was only significant in E2-untreated cows. In contrast to cortisol and progesterone, mean LH values decreased in all animals during stress, but the decline was not significant. However, significantly lower mean LH values were seen at the end of the stress period comparing to values before stress. In cows without stress, E2 treatment had no significant effect on mean values of all three hormones analyzed. From our results it can be concluded that in ovariectomized cows (a) acute stress increases cortisol and progesterone secretion but decreases LH release and (b) the stress induced adrenocortical and pituitary responses were clearly attenuated under the influence of estradiol.

Predictivity of uterine artery, arcuate artery, and intraovarian artery Doppler indices measured on the day of human chorionic gonadotropin injection on pregnancy outcomes

The uterine, arcuate, and intraovarian blood flow measurements by transvaginal color doppler ultrasonography on the day of hCG injection in 46 women undergoing treatment by IVF at Aegean University Family Planning and Infertility Research and Treatment Center were evaluated. In the pregnant group, average uterine and arcuate arteries blood flow resistance values were lower than those in nonpregnant women.

Alternate day and daily administration of GnRH antagonist may prevent premature luteinization to a similar extent during FSH treatment

This randomized controlled trial was designed to evaluate whether a GnRH antagonist given every other day could prevent premature luteinization in women undergoing IVF/ICSI treatment. A total of 73 women receiving ovulation stimulation IVF cycles with recombinant FSH were allocated randomly on cycle day 7 to GnRH antagonist ganirelix in multiple doses (0.25 mg each), either daily (n = 37 women, group 1) or every other day (n = 36 women, group 2) until the day of HCG administration. Serum FSH, LH, estradiol and progesterone values showed similar trends in the two groups. During FSH stimulation, 13 (35%) of the women in group 1 had premature LH rises (> or = 10 IU/l) of which eight (22%) were after the start of antagonist administration. In group 2 there were 14 (39%) LH rises during FSH stimulation of which 10 (28%) were after the start of antagonist administration. Luteinization (serum progesterone >2 ng/ml) occurred in only one woman in each group overall (3%). A significantly smaller total dose of the antagonist was used in group 2 than in group 1 (P < 0.001). The study did not have power to evaluate differences in total dose of FSH, number of oocytes recovered and clinical pregnancy rate, all of which appeared similar in the two groups. Whether alternate day is as effective as daily administration of ganirelix in preventing premature luteinization should be addressed in a non-inferiority trial powered to evaluate live birth rate.