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Pedometer readings for estrous detection and as predictor for time of ovulation in dairy cattle.

The objective of this study was to study the relationship between increase in number of steps measured by pedometers, behavioral estrous parameters and time of ovulation, in order to investigate whether the number of steps can be used as a tool for estrous detection and as a predictor for time of ovulation. In total, 63 ovulations were observed in 43 Holstein-Friesian cows. Different behavioral signs of estrus were observed at 3h intervals. Cows were equipped with pedometers, which stored number of steps in 2h time periods and pedometer estrus alerts were defined using different algorithms and thresholds. The percentage of behavioral estruses also detected by pedometers measurements, ranged between 51 and 87% for all estrous periods. When only estrous periods where taken into account in which more than one animal was in estrus, detection percentages increased up to 95%. Number of steps taken during the estrous period was higher when more animals were in behavioral estrus at the same time, and number of steps taken during the estrous period was also higher for primiparous cows compared to multiparous cows. Ovulation occurred 29.3+/-3.9h after onset of increased number of steps (ranging between 39 and 22 h) and 19.4+/-4.4h after the end of increased number of steps (ranging between 35 and 12h). The intervals were not influenced by the number of animals that were in estrus at the same time or by parity. In conclusion, pedometers can detect estrus accurately and appear to be a promising tool for prediction of ovulation and hence could be a tool for improving fertilization rates.

Algorithms↗

Short term suppression of follicular recruitment and spontaneous ovulation in the cat using levonorgestrel versus a GnRH antagonist.

Suppression and subsequent rebound of ovarian activity using a progestin (levonorgestrel; Norplant) versus a GnRH antagonist (antide) was assessed in the domestic cat via fecal estradiol and progesterone metabolite analyses. Following an initial dose-response trial, queens were assigned to one of four treatments: (1) antide, two 6 mg/kg injections 15 days apart (n = 8 cats); (2) levonorgestrel, six silastic rods (36 mg levonorgestrel/rod) implanted for 30 days (n = 8); (3) control injections (n = 5); and (4) control implants (n = 5). Steroid metabolites were quantified from daily fecal samples for 90 days before, 30 days during, and 90 days after treatment. Antide and levonorgestrel inhibited estrous cyclicity in contrast to continued cyclicity in controls. Cats already at estradiol baseline in antide (n = 7) and levonorgestrel (n = 4) groups remained inhibited during treatment. In females with elevated estradiol levels at treatment onset (Day 0), a normal estradiol surge was completed before concentrations declined to baseline (approximately Days 5-7) and remained suppressed throughout the remaining treatment period. Additionally, 56% of treatment animals exhibited at least one spontaneous ovulation during the pre-treatment period, but no female ovulated during treatment with levonorgestrel or antide. Antide-treated cats exhibited lower (P < 0.05) baseline estradiol concentrations during treatment compared to pre- and post-treatment. In contrast, levonorgestrel induced elevations in baseline estradiol following treatment compared to pre- and during treatment intervals. Control females showed no change (P > 0.05) in baseline estradiol throughout the study period. All levonorgestrel and antide cats returned to estrus after treatment withdrawal. Results demonstrate that: (1) both antide and levonorgestrel are effective for inducing short-term suppression of follicular recruitment and ovulation in the cat; (2) inhibition is reversible; and (3) GnRH antagonists and progestins differentially regulate basal estradiol secretion. This study also confirmed a relatively high incidence of spontaneous ovulation in the cat, a species generally considered to be an induced ovulator.

Animals↗

Are germinal inclusion cysts markers of ovulation?

OBJECTIVES: Germinal inclusion cysts (GICs) of the ovary are possible precursor lesions for epithelial ovarian cancer. These cysts have been postulated to form as stigmata of ovulation. It is known that oral contraceptives, breastfeeding, and pregnancy, which decrease lifetime ovulations, confer protection against epithelial ovarian cancer. This study was undertaken to determine if ovarian density of epithelial inclusion cysts corresponds to a woman's frequency of ovulation. METHODS: One hundred two cases of women undergoing incidental oophorectomy at the time of surgery for benign gynecological conditions were interviewed for information relating to ovulation. Review of multiple sections of ovarian tissue was performed to count numbers of GICs. RESULTS: There was a modest correlation between the average number of germinal inclusion cysts and ovulatory age (Spearman's rho = 0.2, P = 0.06). There were fewer GICs in current smokers and ever-users of oral contraceptives; however these associations were not significant (P > 0.1). CONCLUSIONS: This study showed increased numbers of GICs in women of greater ovulatory age, and those who were not current smokers or ever used oral contraceptives. This provides some evidence that GICs may be caused by ovulation. The small number of subjects limited our ability to evaluate associations.

Adult↗

The angiotensin II antagonist saralasin inhibits ovulation in the perfused rat ovary.

OBJECTIVE: Our null hypothesis was that the angiotensin II antagonist saralasin does not reduce the number of ovulations in the rat ovarian perfusion model. STUDY DESIGN: Ovaries from pregnant mare's serum gonadotropin-stimulated immature rats were perfused with nutrient media to which luteinizing hormone and 3-isobutyl-1-methylxanthine had been added to induce ovulation. Test perfusions were treated with saralasin 1 mumol/L (n = 0.5) and compared with controls (n = 5) with the Student t test. Perfusions with both saralasin and angiotensin II and dose-response evaluations were performed. RESULTS: Saralasin-treated ovulations were 6.6 +/- 1.3 (mean + SEM) compared with 18.6 +/- 3.9, p < 0.02. The effects of saralasin could be reversed with the addition of an equimolar amount of angiotensin II. Dose-response evaluations showed a progressive inhibition of ovulation at 10(-8) to 10(-6) mol/L. CONCLUSION: The angiotensin II antagonist saralasin inhibits ovulation in a dose-dependent fashion; this effect is canceled by the addition of equimolar concentrations of angiotensin II.

Angiotensin II↗

The effect of ovulation induction on the concentration of maternal serum relaxin in twin pregnancies.

OBJECTIVE: Our purpose was to determine the effects of fetal number, various ovulation induction treatments, and placental hormones on the concentration of maternal serum relaxin. STUDY DESIGN: The concentrations of relaxin, human chorionic gonadotropin, estriol, and alpha-fetoprotein were determined in blood samples drawn at 16 to 18 weeks for prenatal diagnosis in 72 singleton and 115 twin pregnancies and analyzed by one-way analysis of variance, correlation analysis, and stepwise multiple linear regression of the log-transformed data. RESULTS: The maternal serum concentrations of each of the four measured hormones were significantly higher in the twin pregnancies than in the singleton pregnancies: 1.4-fold for relaxin, 1.9-fold for human chorionic gonadotropin, 1.9-fold for estriol, and 2.2-fold for alpha-fetoprotein (all p < 0.01). The concentrations of each of the four hormones were significantly correlated with each of the others and with the number of fetuses (p < 0.01), except that estriol was not significantly correlated with human chorionic gonadotropin. The serum relaxin concentration in twin pregnancies after treatment with follicle-stimulating hormone and luteinizing hormone (menotropins) (n = 10) was 3.3-fold that in twins resulting from spontaneous ovulation (n = 89, p < 0.01). In twins resulting from in vitro fertilization or gamete intrafallopian transfer (n = 9) the serum relaxin concentration was 2.6-fold higher than in twins resulting from spontaneous ovulation (p < 0.01). The effect of clomiphene citrate (1.2-fold, n = 7) failed to reach statistical significance. CONCLUSIONS: The second fetus causes a 1.4-fold increase in the concentration of maternal serum relaxin in twin pregnancies. Induction of ovulation with menotropins causes an additional 3.3-fold increase, whereas in vitro fertilization or gamete intrafallopian transfer treatment causes an additional 2.6-fold increase over that seen in twin pregnancies that followed spontaneous ovulation.

Chorionic Gonadotropin↗

Saralasin-induced inhibition of ovulation in the in vitro perfused rat ovary is not replicated by the angiotensin II type-2 receptor antagonist PD123319.

OBJECTIVE: Our aim was to explain the effect of the nonspecific angiotensin II antagonist saralasin and the specific angiotensin II type-2 receptor antagonist PD123319 on ovulation. STUDY DESIGN: Saralasin, 1 micromol/L (n = 5), and PD123319 10 micromol/L (n = 6), were administered to in vitro perfused rat ovary. Prostaglandin (prostaglandin E2, prostaglandin F2alpha, 6-keto-prostaglandin F1alpha), hydroxy-eicosatetraenoic acid (12-hydroxy-eicosatetraenoic acid, 15-hydroxy-eicosatetraenoic acid), estradiol, and progesterone levels in the perfusate and the ovulation rate were compared (Mann-Whitney U test) with controls. RESULTS: Saralasin significantly (P < .01) inhibited the ovulation rate (3.0 +/- 1.4) versus control (13.1 +/- 1.0) and reduced prostaglandin E2 (at 3 hours P < .01 and 20 hours P < .05) and 6-keto-prostaglandin F1alpha (at 20 hours P < .05) levels. Saralasin did not alter prostaglandin F2alpha, hydroxy-eicosatetraenoic acids, or steroid levels. PD123319 decreased 15-hydroxy-eicosatetraenoic acid levels at 3 hours (P < .05) but had no effects on other eicosanoids, steroid levels, or the ovulation rate. CONCLUSION: Angiotensin II plays an important role in ovulation in the rat and is associated with ovarian prostaglandin synthesis. This effect is not selectively regulated via the angiotensin II type-2 receptor.

Angiotensin Receptor Antagonists↗

A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction.

OBJECTIVE: To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. DESIGN: Prospective randomized trial. SETTING: Infertility clinic in a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. INTERVENTION(S): The women were assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities. RESULTS(S): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group. CONCLUSION(S): The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.

Adult↗

Subcutaneously administered Repronex in oligoovulatory female patients undergoing ovulation induction is as effective and well tolerated as intramuscular human menopausal gonadotropin treatment.

OBJECTIVE: To determine the efficacy and safety of Repronex SC as compared with Repronex IM and Pergonal IM in patients undergoing ovulation induction. DESIGN: Randomized, open-label, multicenter, parallel group study. SETTING: Ten academic and private fertility clinics with expertise in ovualtion induction. PATIENT(S): Premenopausal anovulatory and oligoovulatory females (n = 115) undergoing ovulation induction. INTERVENTION(S): Down-regulation with leuprolide acetate followed by up to 12 days of treatment with gonadotropins and hCG administration and luteal phase progesterone support. MAIN OUTCOME MEASURE(S): Percentage of patients ovulating; percentage of cycles with follicular development meeting criteria for hCG administration; number of follicles recruited per cycle meeting hCG criteria; peak serum E(2) levels; rates of chemical, clinical and ongoing pregnancies; adverse events; injection-site pain scores. RESULT(S): There was no statistically significant difference in the percentage of women who ovulated among the treatment groups. However, Repronex SC was significantly more effective than Pergonal IM in producing follicular development in patients who met hCG criteria. There were no significant differences in clinical, ongoing, or continuing pregnancy rates or in multiple pregnancies among the treatment groups. No differences were found in the safety assessments, proportions or seriousness of adverse events or treatment discontinuations. Also, there were no differences between the three treatment groups in patient-recorded scores of injection-site pain or injection-site reactions. CONCLUSION(S): Repronex SC is as efficacious and well tolerated as Repronex IM or Pergonal IM in ovulation induction. Self-administration of Repronex SC provides a convenient treatment alternative to daily IM injections.

Adult↗

Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome.

OBJECTIVE: To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. DESIGN: Case series. SETTING: Outpatient. PATIENT(S): Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. INTERVENTION(S): Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. MAIN OUTCOME MEASURE(S): Resumption of menses, presumptive ovulation, and pregnancy. RESULT(S): Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. CONCLUSION(S): Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.

Adult↗

The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxide synthase levels and ovulation.

OBJECTIVE: To determine the reproductive effects in mice of the deletion of the tyrosine kinase domain of the Ron receptor. DESIGN: Controlled animal studies. SETTING: Academic research environment. ANIMAL(S): Immature mice with deletion of the tyrosine kinase domain of the Ron receptor (TK-/-) at 22-30 days of age and adult black Swiss female mice at 5-6 weeks of age. INTERVENTION(S): Hormonal stimulation of immature female TK-/- animals to induce ovulation. MAIN OUTCOME MEASURE(S): Ovulation rates measured by counting the total number of cumulus oocyte complexes in the ampullar region of the murine oviduct after hormonal stimulation. Western blot analysis measured murine ovarian protein levels of endothelial and inducible nitric oxide synthase (iNOS). Immunohistochemical analysis localized iNOS in the developing murine ovarian follicle. RESULT: Immature TK-/- mice (22-30 days) ovulate significantly fewer cumulus oocyte complexes. Western blot analyses demonstrated increased levels of iNOS before and after ovulation compared with controls. Conversely, endothelial nitric oxide synthase levels were similar and remained constant during corresponding time periods. Immunohistochemical analyses demonstrated a significant increase in iNOS staining throughout the ovary in TK-/- mice with a significant amount of iNOS in granulosa cells surrounding the oocyte when compared with controls. CONCLUSION(S): The increased level of nitric oxide in the TK-/- mice is likely due to an elevated level of iNOS, which may contribute to a decrease in the size of the ovaries and ovulation rates of immature TK-/- animals.

Animals↗

The value of ultrasound, gonadotropin, and estradiol measurements for precise ovulation prediction.

The exact prediction of ovulation is becoming more important in the management of infertile women. Graafian follicle diameter, measured by ultrasound and plasma follicle-stimulating hormone, luteinizing hormone, and estradiol levels were compared retrospectively as predictors of ovulation in 14 normal women in whom ovulation was dated by conventional ultrasound techniques. Follicle diameter was found to be a better predictor of the anticipated time of ovulation than endocrine estimations for short-term as well as long-term predictions in normal women. The relationship between follicle diameter and plasma estradiol for each day before ovulation was linear but contained a great amount of scatter, suggesting that the assessment of normality of follicular development in infertile women may not be possible with the use of these parameters.

Estradiol↗

Ovulation stigma and concentration of progesterone and estradiol in peritoneal fluid: relation with fertility and endometriosis.

The relationship between the presence or absence of an ovulation stigma and (1) the fertility status, (2) the incidence of endometriosis, (3) the concentration of progesterone and estradiol in the peritoneal fluid, and (4) the blood levels of luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol in 21 fertile and 45 infertile patients who underwent a laparoscopy in the early (n = 48) or late luteal phase (n = 18) was investigated. An ovulation stigma was observed in about half of the patients, irrespective of their fertility status (past and subsequent), the presence of endometriosis, or the time of the luteal phase. Progesterone and estradiol concentrations in the peritoneal fluid were highest in the early luteal phase, but they were not correlated with the presence or absence of an ovulation stigma. No significant differences were observed in peripheral hormone levels between women with and those without an ovulation stigma nor between women with high or low concentrations of progesterone in the peritoneal fluid. From the data, it is concluded that hormone assays are of no aid in the diagnosis of the luteinized unruptured follicle syndrome and that the absence of an ovulation stigma on laparoscopic examination cannot be equated with the luteinized unruptured follicle syndrome.

Adult↗

Age and follicular phase estradiol are better predictors of pregnancy outcome than luteinizing hormone in menotropin ovulation induction for anovulatory polycystic ovarian syndrome.

OBJECTIVE: To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction. DESIGN: Retrospective analysis of all available data over 2 years. SETTING: Tertiary referral ovulation induction clinic. SUBJECTS: Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction. MAIN OUTCOME MEASURES: Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or > or = 20 weeks' amenorrhea. RESULTS: Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending < 20 weeks, 105 pmol/L (28.6 pg/mL) and for > or = 20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 < or = 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2.

Abortion, Spontaneous↗

The antiprogestin RU486 delays the midcycle gonadotropin surge and ovulation in gonadotropin-releasing hormone-induced cycles.

OBJECTIVE: To investigate whether the antiprogestin RU486 acts primarily on the hypothalamus to delay the midcycle gonadotropin surge and thus gain insight into the site(s) of action of P in the control of ovulation. DESIGN: Prospective, crossover, single-blinded clinical study. SETTING: Outpatient clinic in an academic research environment. PATIENTS: Women with hypothalamic amenorrhea. INTERVENTIONS: RU486 or a placebo was given orally at a low dose of 1 mg/d for 5 days, starting when the dominant follicle reached 14 to 16 mm, to women with hypothalamic amenorrhea undergoing ovulation induction with GnRH pulses of unvarying frequency and dose. Blood samples and ovarian ultrasounds were obtained daily in the late follicular phase and every 3 to 4 days in the remainder of the cycle. MAIN OUTCOME MEASURES: Follicular diameter and plasma levels of LH, FSH, E2, and P. RESULTS: RU486 consistently delayed the timing of the midcycle gonadotropin surge and ovulation. Gonadotropin and steroid levels were suppressed during RU486 treatment, but follicular growth progressed normally in most patients. CONCLUSIONS: RU486 does not act primarily on the hypothalamus to delay ovulation. Rather, this compound appears to antagonize P at the pituitary level to suppress gonadotropin and steroid hormone secretion. P may thus act on the pituitary, independent of any hypothalamic effects, to regulate the timing of the midcycle gonadotropin surge and ovulation.

Adult↗

Luteal dysfunction in ovulation induction: the role of repetitive human chorionic gonadotropin supplementation during the luteal phase.

Several studies have indicated that ovulation induction with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or clomiphene citrate (CC) is associated with luteal phase defect. To assess the efficiency of luteal support by hCG to an infertile population undergoing ovulation induction, with CC/hCG or hMG/hCG, we have randomly administered 2500 IU hCG intramuscularly on days 3, 6, and 9 after ovulation induction by 10,000 IU of hCG to 74 patients on 265 treatment cycles. As controls served 357 ovulation induction cycles in the same 74 patients. The treatment cycles were randomly alternated with control cycles so that each patient served as her own control. However, the mean +/- standard deviation (SD) midluteal P was 38.1 +/- 10.8 ng/ml in the study group versus 15.7 +/- 10.5 ng/ml in the control group (P less than 0.001). Luteal phase length was 15.4 +/- 1.5 days in the treatment group versus 12.1 +/- 1.7 in the control group (P less than 0.01). In the treatment group, 64.8% of the patients achieved pregnancy (27% pregnancies/treatment cycle) versus 47.3% in the control group (11.5% pregnancies/control cycle) (P less than 0.01). The pregnancy wastage rates (including abortions and "chemical" pregnancies) were 30.6% in the treatment group versus 56% in the control group (P less than 0.01). We conclude that repetitive hCG administration may be an efficient luteal support in infertile patients undergoing ovulation induction.

Adult↗

Sequential bilateral adnexal torsion after a single cycle of gonadotropin ovulation induction with intrauterine insemination.

OBJECTIVE: To report a rare case of sequential bilateral adnexal torsion in a pregnant woman after a single cycle of gonadotropin ovulation induction with IUI. To review the literature with regards to the causation and aspects of the management of adnexal torsion, particularly after assisted conception. DESIGN: Case report. SETTING: Fertility department within a teaching hospital. PATIENT(S): A 35-year-old woman with a twin pregnancy after a cycle of gonadotropin ovulation induction and IUI. INTERVENTION(S): Gonadotropin ovulation induction with IUI; two laparotomies, salpingo-oophorectomy, stabilization of adnexa with stay suture. RESULT(S): Continuation of pregnancy until 37 weeks gestation with the abdominal delivery of healthy twins. CONCLUSION(S): The case of a woman with a multiple pregnancy and ovarian hyperstimulation syndrome after ovulation induction and IUI who developed sequential bilateral adnexal torsion is used to illustrate the risk factors and management options for adnexal torsion. Physicians should be aware of the increased incidence of adnexal torsion in the rising number of women undergoing ovulation induction in order to effect early surgical intervention and adnexal salvage. Consideration should be given to the anchoring of bulky adnexae to prevent torsion recurrence.

Adnexal Diseases↗

The role of luteinizing hormone in folliculogenesis and ovulation induction.

OBJECTIVE: To review the physiologic, pathophysiologic, and clinical roles of LH in follicle and oocyte development and maturation and to assess the effects of LH content in exogenous gonadotropin preparations used for ovulation induction. DESIGN: Critical review of the scientific literature devoted to folliculogenesis. Evaluation of comparison studies that used different gonadotropin preparations for ovulation induction. CONCLUSION(S): Folliculogenesis and oocyte maturation are complex processes that require the action of both LH and FSH. Luteinizing hormone is essential to provide the androgen substrate for estrogen synthesis, which in turn contributes to oocyte maturation and may play a relevant role in optimizing fertilization and embryo quality. Although the excessive LH secretion that is present in some disorders is detrimental to reproductive function, this is not applicable to ovulation induction with hMG because this menotropin does not increase daily plasma LH levels. The results of ovulation induction with hMG or FSH-only regimens did not differ in studies conducted in patients with polycystic ovary syndrome and in most studies conducted in ovulatory women undergoing assisted reproductive techniques; conversely, hMG was clearly superior to purified FSH for the treatment of hypogonadotropic hypogonadism. Miscarriage rates were not affected by the use of hMG. Thus, low but detectable LH concentrations positively influence the outcome of ovulation induction in patients with ovulatory disorders and women undergoing assisted reproductive techniques.

Estrogens↗

Gonadotropin releasing hormone analogs for female contraception by inhibition of ovulation.

One hundred and one healthy regularly ovulating women used two superactive GnRH agonists, Buserelin and Nafarelin, for contraception for 3-26 months. The superagonists were administered once daily by a nasal spray. The treatment was initiated on one of the first 3 days of the menstrual cycle. Seventy-one volunteers used 200, 400 or 600 micrograms of Buserelin for contraception for 3-26 months. Normal ovulation was disturbed in all but 3 of 628 treatment months. No pregnancy occurred. Fifty-three women had regular or sparse menstrual-like bleedings during treatment while 18 developed amenorrhea. Normal ovulation and fertility rapidly returned after cessation of therapy. Thirty women received 125 or 250 micrograms of Nafarelin intranasally once daily for 3 months. The treatment consistently inhibited ovulation without serious side effects. The inhibition of ovulation by prolonged continuous intranasal GnRH agonist therapy is a promising new lead to peptide contraception in women.

Administration, Intranasal↗