Experience with the induction of ovulation.
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Abortion, Spontaneous↗
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Correlation between preovulatory serum estradiol and midluteal progesterone levels during induction of ovulation with Clomid and HCG.
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Adult↗
Induction of ovulation and multiple pregnancies.
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Adult↗
[Therapeutic induction of ovulation: towards the replacement of hCG with LH].
Ovulation has exclusively been triggered with Human Chorionic Gonadotropin (hCG) since the earlier times of follicular stimulation with Pregnant Mare Serum Gonadotropins (PMSG). hCG was chosen in regard of its LH-like effect, when isolated or purified human LH was not available. hCG, however, is not the physiologic hormone for ovulation triggering and shows many discrepancies in pharmacokinetics and bio-availability with LH, accounting for the permanent risk for ovarian hyperstimulation syndrome (OHSS) following hCG administration. Human recombinant LH should become available in the coming years, but it is at present possible to trigger ovulation in hMG--stimulated patients with their own pituitary LH, using a short-acting GnRH agonist. Literature shows that this method of triggering ovulation in in vitro fertilization (IVF) cycles as well as in non IVF cycles results in a satisfactory ovulatory process and pregnancy rates comparable to those observed following hCG administration. More over, triggering ovulation with endogenous LH considerably reduces the risks for OHSS, and perhaps for multiple pregnancies. Optimum posology for each GnRH agonist available remains to be evaluated to minimize the occurrence of short luteal phases following ovulation triggering with endogenous LH.
Biological Availability↗
Effect of constant administration of a gonadotropin-releasing hormone agonist on reproductive activity in mares: induction of ovulation during seasonal anestrus.
The potential of a gonadotropin-releasing hormone (GnRH) agonist (goserelin acetate), delivered constantly for 28 days via a subcutaneous depot, to induce ovulation in seasonally anestrous mares, was investigated. Two experiments were conducted, in which a range of doses (30 to 240 micrograms/mare/d) was examined. Mares were selected on the basis of lack of substantial follicular development (follicle diameter < 20 mm determined ultrasonically) and low serum concentrations of luteinizing hormone (LH) and progesterone. Constant administration of the GnRH agonist-induced ovulation in anestrous mares, but a dose-response relation was not observed. Furthermore, with identical doses tested in consecutive or alternate years, considerable variation was observed in the ovulatory response. In general, ovulation in all treated mares was accompanied by increased circulating concentrations of LH and a decrease in follicle-stimulating hormone values. Ovulation was preceded by an increase in estradiol and LH concentrations. In mares in which ovulation did not occur, concentration of LH increased during agonist treatment, whereas that of follicle-stimulating hormone either increased or did not change. It was concluded that constant administration of GnRH agonists may induce ovulation in mares during seasonal anestrus; however, percentage of mares ovulating and the lack of reproducibility of effect indicate that this approach is inappropriate for use as a reliable method to manipulate breeding activity in commercial broodmares.
Anestrus↗
A nomogram to predict the probability of live birth after clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.
OBJECTIVE: To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate (CC). DESIGN: Prospective longitudinal single-center study. SETTING: Specialist academic fertility unit. PATIENT(S): Two hundred fifty-nine couples with a history of infertility, oligoamenorrhea, and normal follicle-stimulating hormone (FSH) concentrations who have not been previously treated with any ovulation-induction medication. INTERVENTION(S): 50, 100, or 150 mg of oral CC per day, for 5 subsequent days per cycle. MAIN OUTCOME MEASURE(S): Conception leading to live birth after CC administration. RESULT(S): After receiving CC, 98 (38%) women conceived, leading to live birth. The cumulative live birth rate within 12 months was 42% for the total study population and 56% for the ovulatory women who had received CC. Factors predicting the chances for live birth included free androgen index (testosterone/sex hormone-binding globulin ratio), body mass index, cycle history (oligomenorrhea versus amenorrhea), and the woman's age. CONCLUSION(S): It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram. Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility. Alternative first line of treatment options could be considered for some women who have limited chances for success.
Abortion, Spontaneous↗
Control and induction of ovulation in cattle.
The control and induction of ovulation in cattle are discussed with particular reference to use of progesterone-impregnated coils in heifers and beef cows. Progesterone treatment for 14 days was required to obtain precise onset of oestrus. With 7, 9 or 12 days of progesterone treatment a luteolytic agent in the form of a prostaglandin (PG) or oestradiol benzoate had to be used. Fertility was normal after treatment durations of 7, 9 or 12 days, but fertility after 14-day treatment requires further testing. The progesterone coil was not effective in maintaining luteal-phase levels of progesterone throughout a 12-day treatment and increasing the concentration of progesterone in the coil from 4 to 20% was not effective in elevating the progesterone concentrations in blood. When progesterone concentrations dropped below approximately 1.5 ng/ml the basal level of LH began to rise before removal of the coil. A 2-fold rise in the basal level of LH was observed following the removal of the progesterone coil. This early rise in LH was absent in cows which did not ovulate after they were given a 12-day progesterone treatment and GnRH 24-36 h after removal of coils to induce the main LH peak. Absence of this early rise suggests that frequency and amplitude of episodic LH release were inadequate in the post-partum anovulatory period. Ovariectomy in the early post-partum period was not followed by an abrupt LH release.
Animals↗
Induction of ovulation in polycystic ovary: human menopausal gonadotropin or human urinary follicle stimulating hormone?
One group of 21 and one group of 22 anovulatory women with polycystic ovaries (PCO) underwent induction of ovulation with human urinary follicle stimulating hormone (HU-FSH)/human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG)/HCG, respectively. No statistically significant differences in ovulation rate were found between patients treated with HU-FSH (95.2%) and those treated with HMG (100%). Eight (38.1%) and 11 (50.0%) patients conceived, six (28.5%) and eight (36.3%) delivered, and two (9.5%) and three (13.6%) aborted with HU-FSH and HMG, respectively. No multiple pregnancies occurred. Serum 17 beta-estradiol (E2) levels and the number of maturing follicles prior to HCG injection were significantly higher with HU-FSH than HMG, while there were no differences in the diameter of the dominant follicle before HCG. Ovarian hyperstimulations were discovered more frequently after HU-FSH/HCG (40%) than HMG/HCG treatments (22.2%). These data do not confirm an effective advantage in the use of HU-FSH in ovulation induction in cases of PCO.
Anovulation↗
Clinical pregnancy and male subfertility; the ESHRE multicentre trial on the treatment of male subfertility. European Society of Human Reproduction and Embryology.
Ovulation induction alone, and ovulation induction in conjunction with one of four assisted procreation methods [intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF)] were tested as a treatment for male infertility in a prospective randomized trial. The trial when completed had generated data on 499 cycles from 346 patients. There was overwhelming evidence that some form of assisted procreation was beneficial, when compared to the spontaneous natural conception rate, which is generally assumed to be between 0.01 and 0.02 for male infertility. There was also firm evidence that IUI, GIFT or IVF (mean per cycle pregnancy rate 0.212) were superior to the remaining two treatments of IPI and ovulation induction alone (mean per cycle pregnancy rate 0.068). Duration of infertility and a diagnosis of endometriosis were the most important (adverse) pre-treatment factors detected.
Endometriosis↗
Birth weight in pregnancies after induction of ovulation with pituitary gonadotrophins.
Birth weights offer a means of determining normality of babies born after induction of ovulation with human pituitary gonadotrophins. A study of 62 patients treated under the auspices of the Australian Human Pituitary Advisory Committee shows that birth weights of the babies were not significantly different from those in two large Australian obstetric populations. Multiple pregnancies are more common after ovulation induction. Birth weights in twins are approximately 85% of those in singleton pregnancies.
Abruptio Placentae↗
Induction of ovulation monitored by ultrasound.
Eighty menstrual cycles were induced by the administration of human menopausal gonadotropin (hMG), and the induction of ovulation was evaluated by serial ultrasound scanning. Ovulation occurred in 57 of these cycles, and pregnancy occurred in 17 patients. No pregnancy occurred if the follicle size was below 15 mm at the time that human chorionic gonadotropin (hCG) was administered. A 15-mm follicle size is, therefore, regarded as a minimum size for a mature ovum. Multiple follicles were present in seven of the cycles where pregnancy occurred, but only two patients had multiple pregnancies. Ovarian hyperstimulation (OHS), which is characterized by cystic ovarian enlargement of greater than 5 cm after ovulation, was present in 25 cycles. This is a considerably higher incidence than previously documented, but since it is not possible to predict reliably its occurrence, and in no patients were the symptoms severe, it is considered an acceptable and inevitable sequela of ovulation induction. The present role of ultrasound is to establish whether the ovary responds to gonadotropin stimulation, to ensure that the follicle has reached a minimum size, to determine the number of preovulatory follicles to inform better the patient about the possibilities of multiple pregnancies, to establish that ovulation has occurred after administration of hCG, and to document the presence or absence of OHS.
Estrogens↗
The pregnancy rates with intrauterine insemination (IUI) in superovulated cycles employing different protocols (clomiphen citrate (CC), human menopausal gonadotropin (HMG) and HMG+CC) and in natural ovulatory cycle.
OBJECTIVE: To compare the result of IUI in infertile couples with different protocols of induction ovulation. METHODS: In a retrospective study, 209 infertile couples with different diagnosis (unexplained, male factor, endometriosis, tubal disease, ovulatory dysfunction and multifactorial infertility) were subjected to different protocol of induction ovulation: 50-100 mg CC in day 2-6, 50 mg CC in day 2-6 + 2 amp HMG in day 5, 7, 9, 11, and 2 amp HMG per day. Natural ovulatory cycle + IUI was used for sperm stored patients. 441 consecutive cycles of IUI was performed 36-40 hours after HCG injection. The data were analysed with student T-test and Mann-Whitney test. The significance was defined as P<0.005. RESULTS: Thirty one pregnancies (7% per cycle, 15% per patient) occurred. One pregnancy occurred (pregnancy per cycle was 2% and per patient was 12%) in 8 patients undergoing 37 cycles of IUI with natural ovulation. The result with CC in 27 patients undergoing 41 cycles IUI was 2 pregnancies (4% per cycle, 7% per patient). In 129 patients receiving 283 cycles of IUI with CC+HMG 21 pregnancies occurred (7% per cycle, 16% per patient). In 35 patients receiving 80 cycles of IUI with HMG 8 pregnancies occurred (9% per cycle, 23% per patient). CONCLUSION: The method chosen for ovulation induction had a critical bearing on the success of IUI. The result of IUI will be better by using induction ovulation compared to natural ovulatory cycle. In our programme the combined use of HMG+IUI yielded a higher rate of pregnancy rate compared with CC+IUI, CC+HMG+IUI and natural ovulatory cycle+IUI.
Clomiphene↗
Chronic low-dose follicle-stimulating hormone compared with clomiphene/human menopausal gonadotropin for induction of ovulation.
Concurrent administration of clomiphene can reduce the amount of gonadotropins required for induction of ovulation. Recently, follicle-stimulating hormone (FSH) administered in a chronic, low-dose fashion has been reported to give satisfactory pregnancy rates. We compared the conventional clomiphene/human menopausal gonadotropin (hMG) with the chronic, low-dose FSH regimen for induction of ovulation in 87 patients over 110 cycles. The clomiphene/hMG regimen required half the amount of gonadotropin compared to the chronic FSH regimen to achieve follicular maturation. Despite the reduced amount of gonadotropin, the clomiphene/hMG regimen induced a mean fourfold higher level of estradiol production and was associated with significantly greater numbers of large and intermediate-sized follicles compared to the chronic FSH regimen. The proportion of clomiphene/hMG cases with multifollicular development and overstimulation was therefore high (30%). In contrast, the chronic FSH regimen, despite requiring larger amounts of gonadotropin and longer periods of treatment, resulted in unifollicular development, low rates of overstimulation and improved pregnancy rates. We conclude that although clomiphene can reduce the requirement for gonadotropins, the relative safety and effectiveness of the chronic low-dose FSH regimen makes it the method of choice for ovulation induction.
Adult↗
[Induction of ovulation with subcutaneous pulsatile administration of human menopausal gonadotropin].
Induction of ovulation with subcutaneous pulsatile (every 90 min.) administration of HMG (Pergonal) 75 or 150 IU/day using a portable pump (Nipro SP-3I) was performed in 3 PCO patients (6 cycles), 4 first grade amenorrhea (Am-I) patients (7 cycles) and 4 Am-II patients (4 cycles). All patients ovulated except one cycle of Am-I patients and one PCO woman conceived. In regard to the duration of administration and the total dose of HMG until ovulation, the administration of 150 IU/day (M +/- SD=15.2 +/- 5.0 days, 2280 +/- 774 IU) is superior to 75 IU/day (39.5 +/- 11.4 days, 3900 +/- 1357 IU), and there was no significant difference between this method and the daily intramuscular injection of HMG. The group treated with HCG in the luteal phase revealed a longer luteal phase (14.0 +/- 2.3 days) than the nontreated group (12.6 +/- 1.5 days). Ovarian hyperstimulation was observed in one case and subsided spontaneously after admission. There were no other side effects. In conclusion, this method has the following advantages: A high ovulation rate, comparable with daily intramuscular administration. It is a less painful procedure than daily intramuscular injection. It is possible for the patient to lead normal life, insertion and removal being easily done by herself.
Adult↗
["Step protocols"].
Within the last decade, induction of ovulation with gonadotrophins, specially for patients with polycystic ovary syndrome, has been extensively revisited. On the basis of physiological concepts as the FSH threshold, the FSH window and the hypersensitivity to FSH of selected dominant follicle, news protocols have been described: step-up protocol, step-down, sequential protocol. In this article, their efficacy and safety are discussed. It is presumed that these new protocols would open a new way in the management of ovulation induction.
Clinical Protocols↗
A role for thyroid hormone in the induction of ovulation and corpus luteum function.
We have previously demonstrated that thyroid hormone synergizes with follicle-stimulating hormone (FSH) to exert stimulatory effects on granulosa cell differentiation and function, suggesting that it plays a physiological role in amplifying FSH-mediated differentiation of granulosa cells. The adequate differentiation of these cells, followed by normal follicle development, is indispensable for ovulation and subsequent corpus luteum formation. Thus, in the present studies, the clinical implications of thyroid hormone in the induction of ovulation and corpus luteum function were investigated. Serum levels of total 3,5,3'-triiodothyronine (T3) and total thyroxine (T4) as well as free T3 and T4 were significantly lower in patients with weight loss amenorrhea compared to normal cycling women. Although no ovulation was induced by clomiphene therapy when the serum T3 levels were less than 80 ng/dl, the rate of ovulation induced by clomiphene increased in parallel with the augmentation of serum T3 levels. This suggests that an adequate circulating level of thyroid hormone is one of the factors responsible for successful induction of ovulation by clomiphene citrate. Furthermore, the short luteal phase and insufficient progesterone secretion observed in patients with subclinical hypothyroxinemia were not improved by clomiphene therapy alone, but were improved markedly by combined treatment with thyroid hormone replacement and clomiphene citrate. These data imply that concomitant clomiphene treatment with thyroid hormone replacement therapy is of a great value not only for ovulation induction, but also for the treatment of luteal-phase defect in patients with subclinical hypothyroxinemia.
Adolescent↗
A comparison between a standard and reduced dose of D-Trp-6-luteinizing hormone-releasing hormone administered after pituitary suppression for in-vitro fertilization.
A randomized prospective study was undertaken to compare low and standard luteinizing hormone-releasing hormone agonist (LHRHa) dosage used in combination with gonadotrophins in ovarian stimulation for in-vitro fertilization (IVF). A total of 42 ovulatory patients with mechanical infertility were administered 0.5 mg/day LHRHa (Decapeptyl) from day 21 of their cycles for 14 days. Following down-regulation, patients were randomly allocated to continue with the same dose of LHRHa (22 patients, group A) or to receive a lower dose of 0.1 mg/day LHRHa (20 patients, group B) during folliculogenesis. Luteal phase was supported by daily i.m. progesterone (50 mg) injections and human chorionic gonadotrophin (HCG; 1500 IU) every 4 days. Ovarian response, human menopausal gonadotrophin (HMG) dosage used for induction of ovulation, evidence of premature luteinization, and clinical and laboratory IVF outcome, were compared between groups A and B. The two groups were comparable in respect of: age (32.6 +/- 0.7 and 33.0 +/- 0.9 years), HMG dosage (33.0 +/- 1.6 and 36.0 +/- 2.5 ampoules), day of HCG (11.2 +/- 0.3 and 12.2 +/- 0.4), oocytes/patient (13.3 +/- 1.0 and 12.9 +/- 1.3), fertilization rate (68.5 and 65.2%), cleavage rate (95% for both), pregnancy/embryo transfer (32 and 35%) and implantation rate (10.8 and 10.5%), for groups A and B respectively. There was no evidence of premature luteinization or luteolysis in either group. It was concluded that lowering the dose of LHRHa to 0.1 mg/day during folliculogenesis had no adverse effect on ovarian response or clinical results. However, it had no advantage in reducing the HMG dose used for ovulation induction.
Adult↗