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PubMed1987

Induction of ovulation by intermittent intravenous purified follicle-stimulating hormone in polycystic ovarian disease.

IIV FSH was administered to eight women with PCOD to induce ovulation. These patients had been previously treated unsuccessfully with CC or IM gonadotropins. The drug was administered by a pump at 120-minute intervals. Dosage was 1 ampule Metrodin (75 IU of FSH less than 0.11 IU of LH)/day. Eight cycles of treatment were effected. With the IIV regimen, ovulation rate was 75% (six cycles). Two multiple pregnancies and one abortion (mola vescicularis) were observed. Preovulatory E2 plasma levels and the number of follicles recruited per cycle varied from 530 to 3800 pg/ml and from 4 to 15, respectively. Maximal follicular diameter was between 16 and 28 mm. LH levels significantly decreased, while FSH levels were unchanged, resulting in a decrease of LH/FSH ratio. It is concluded that the IIV FSH regimen offers an additional modality for the induction of ovulation in PCOD patients. Further clinical trials with alternative regimens are needed, however, to identify the optimal dosage and frequency of administration of the drug.

Adult↗
PubMed1980

Induction of ovulation and pregnancy in twenty-six patients with primary hypogonadotropic amenorrhea.

The methods and results of treatment with human menopausal gonadotropins (hMG) and chorionic gonadotropin (hCG) in 26 patients (mean age 24 years, range 22-35 years) with hypogonadotropic primary amenorrhea and without chromosomal abnormalities are reported. The usual dose of hMG was 225 IU daily until the karyopycnotic index rose to 40% or more and the other clinical parameters revealed sufficient follicular maturation. A dose of hCG was then administered at the rate of 10,000 IU daily for 4 days. In 60 courses of treatment, we obtained 17 pregnancies (28.3%) in 13 patients (i.e., including some second pregnancies), 35 ovulations without pregnancy (58.3%), and seven patients did not respond (11.6%). Three patients who did not respond and who continued the treatment ovulated and became pregnant. Clinical hyperstimulation occurred in three patients on the first course of treatment. Two of them again presented this complication on repetition of treatment despite the precautions taken. Urinary estrogen and pregnanediol measurements on the 7th-11th day after hCG administration revealed considerable hormonal hypersecretion in 19 of 27 courses of treatment. In eight patients the high output of pregnanediol continued during the first 1-2 months of pregnancy and decreased thereafter. The rate of pregnancies seemed to be higher in patients with hypersecretion whereas clinical hyperstimulation did not correlate with the degree of the hormonal output. Pregnancies were all single and uneventful except for one abortion in a patient who was found to have mycoplasma infection. All patients gave birth to normal children and lactated normally. The increased dosage of hCG used in this series is considered to be a decisive factor in the induction of ovulation and the maintenance of pregnancies through the abundant steroid production it induced.

Adult↗
PubMed1989

Clinical experience in the induction of ovulation and pregnancy with pulsatile subcutaneous administration of human menopausal gonadotropin: a low incidence of multiple pregnancy.

The pulsatile subcutaneous administration of human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was used for induction of ovulation in 26 patients with hypothalamic/pituitary amenorrhea or polycystic ovary syndrome (PCO). Ovulation was observed in 116 (90.6%) of 128 treatment cycles, and 15 (16 treatment cycles) of 26 patients became pregnant. All 14 fetuses, excluding two pregnancies interrupted spontaneously at weeks 6 and 9, were singleton conceptions. Ovarian hyperstimulation was observed in 15.6% of treatment cycles. Five patients with PCO who failed to conceive on the hMG regimen also received pulsatile FSH administration. Although ovulation rates in PCO patients did not differ significantly between the hMG (88.1%) and FSH (88.2%) regimens, a significant reduction in the average dose of FSH (P less than 0.05) was observed with pulsatile FSH administration. Furthermore, the number of patients who conceived during the FSH regimen was significantly greater than that found with hMG treatment. The present data demonstrate that pulsatile subcutaneous administration of hMG or FSH is effective in induction of successful ovulation and establishment of singleton pregnancy in patients with various types of anovulatory infertility.

Adult↗
PubMed2001

Induction of follicular growth and ovulation with urinary and recombinant gonadotrophins.

Gonadotrophins have been used since the 1930s. By the 1990s, a pure biological extract of FSH was obtained. The increase in the demand for new assisted reproduction techniques led to the creation of recombinant FSH, 99% pure and highly consistent between batches, with no LH activity, and a high specific activity. In gonadotrophin protocols, follicular growth can be monitored with regular ultrasounds and/or hormonal testing, mainly oestradiol in the follicular phase. In assisted reproduction the adoption of ovulation induction strategies with GnRH analogues, control the endogenous secretion of LH, avoiding cancellations due to an early LH surge, and premature ovulation. Depending on the moment when pituitary suppression starts, there are short, ultra-short and long protocols The use of long protocols not only increases pregnancies and live births, it also allows an easier programming and simplifies IVF treatments. Ovarian stimulation entails some risks such as ovarian hyperstimulation syndrome and multiple pregnancies that can be avoided in many cases with an accurate prediction and an active prevention.

Journal Article↗
PubMed1988

Induction of ovulation with D-Trp6-LHRH combined with purified FSH in patients with polycystic ovarian disease.

Seventeen patients with polycystic ovarian disease (PCOD) and evidence of mild or severe ovarian hyperstimulation syndrome (OHSS) during therapy with CC/hCG, FSH/hCG or hMG/hCG were treated with D-Trp6-LHRH until medical gonadectomy was attained. Under the suppressive therapy with the GnRH agonist (GnRHa) ovulation was induced with FSH/hCG. In 15 out of 17 patients, ovulatory cycles were obtained with this new modality of treatment. Seven patients conceived (3 viable pregnancies and 4 early abortions) after the 1st treatment cycle. Fourteen of the 17 patients demonstrated symptoms of mild OHSS which did not require hospitalization. Only 1 patient developed severe OHSS after the combined treatment. Our results suggest that therapy with GnRHa, especially in its delayed release formulation, is effective for the prevention of severe ovarian hyperstimulation in PCOD patients undergoing treatment with menotropins for the induction of ovulation.

Adult↗
PubMed1996

Induction of ovulation in clomiphene-resistant polycystic ovary syndrome with pulsatile GnRH.

OBJECTIVE: To determine the efficacy of pulsatile GnRH alone and in combination with clomiphene citrate or gonadotropins in a stepwise approach for inducing ovulation in women with clomiphene-resistant polycystic ovary syndrome (PCOS). METHODS: Eighty women with clomiphene-resistant anovulatory infertility and PCOS were given subcutaneous pulsatile GnRH (15 micrograms every 90 minutes) using a portable infusion pump. If no follicular development was seen, clomiphene citrate (100 mg/day for 5 days) was given concurrently with the hormone in the next cycle of treatment. Those who still failed to ovulate regularly were treated with combined pulsatile GnRH with intramuscular gonadotropins (one ampule per day for 5-7 days). RESULTS. Sixty-six of 131 (50%) pulsatile GnRH cycles, 94 of 142 (66%) pulsatile GnRH with clomiphene cycles, and 48 of 69 (70%) pulsatile GnRH with gonadotropin cycles were ovulatory. Monofollicular response (one follicle at least 14 mm on the day of ovulation) occurred in 80.6, 83.9, and 53.6% of cycles, and multifollicular response occurred in 4.8, 3.1, and 21.6% of cycles in the three groups, respectively. Mild ovarian hyperstimulation occurred in one of the 342 cycles. The cumulative conception rate was 30% after three cycles, 60% after six cycles, and 73% after nine cycles. The miscarriage rate was 22% (ten of 45 pregnancies), and 35 women (78%) had live births (33 singletons and two sets of twins). CONCLUSION: The use of subcutaneous pulsatile GnRH alone and in combination with clomiphene citrate or gonadotropins for induction of ovulation in clomiphene-resistant PCOS in a stepwise approach produces a high cumulative conception rate associated with a low rate of multiple pregnancy and ovarian hyperstimulation syndrome.

Adult↗
PubMed1976

The induction of ovulation.

A treatment plan utilizing placebo, cyclical steroid therapy, clomiphene citrate, and human pituitary gonadotropin is outlined for the induction of ovulation in carefully selected potentially fertile women. Such a plan minimizes any risk with the potentially hazardous ovulatory stimulants. A total of 220 patients with secondary amenorrhea were studied and an etiologic basis for the condition was found in 98 (45 per cent). Of the 220, 190 were found suitable for the induction of ovulation, and together with 145 patients with oligomenorrhea and 17 patients with anovulation, entered the treatment plan. Ovulation was successfully induced in 351 of the 352 (99.5 per cent) and pregnancy in 218 (61.9 per cent). The success rates for the agents in the various conditions are presented and discussed.

Amenorrhea↗
PubMed1983

Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: phase I, 1981.

Thirty-one human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) ovulation induction cycles from 25 normally ovulating patients who applied to a program for the Vital Initiation of Pregnancy (VIP) are discussed. Three different categories of serum estradiol (E2) response were found. Serum E2 and progesterone responses were inversely related to the amount of hMG, indicating a patient sensitivity rather than a dosage relationship. Luteinizing hormone levels were suppressed by gonadotropins. Daily evaluation of vaginal smear, cervical mucus, serum E2 determinations, and pelvic ultrasound are necessary for an optimum ovulation induction with gonadotropins. Two successful pregnancies are reported.

Chorionic Gonadotropin↗
PubMed1995

Gonadotrophin induction of ovulation using a step-down dose regimen: single-centre clinical experience in 82 patients.

A total of 82 normogonadotrophic clomiphene-resistant anovulatory patients were treated with exogenous gonadotrophins according to a step-down dose regimen during 234 cycles. In 43 (18%) cycles co-treatment with gonadotrophin-releasing hormone analogues was applied. The initial dose was between 1.5 and 2.5 ampoules (75 IU follicle-stimulating hormone each) per day (dependent on body weight), and decreasing steps of 0.5 ampoules/day were based on sonographic findings. The overall ovulation rate was 91% (213 cycles). The median treatment period was 11 days and a total of 14 ampoules of gonadotrophin were needed. In 131 (62%) of the ovulatory cycles not more than one, and in 208 (98%) cycles not more than two, follicles > or = 16 mm were present on the day human chorionic gonadotrophin was given. A total of 37 pregnancies occurred of which two were twins and one was a triplet (multiple pregnancy rate 8%). The pregnancy rate per cycle was 17% and the cumulative pregnancy rate after 7 months was 47%. The abortion rate was 19%. There were four (1.7%) cases of mild ovarian hyperstimulation, of which none became pregnant. In conclusion, this study shows that the applied step-down regimen for gonadotrophin induction of ovulation can be a safe and effective treatment alternative for patients with clomiphene-resistant anovulation. The duration of ovarian stimulation and the amount of exogenous gonadotrophin required is limited. Pregnancy rates are comparable with those reported for step-up regimens, and a low incidence of complications (i.e. multiple gestation and ovarian hyperstimulation) was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Metformin and polycystic ovary syndrome: a literature review.

Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects women of reproductive age. Anovulation, menstrual irregularities, hirsutism, and infertility are common clinical presentations. Long-term health concerns such as type II diabetes mellitus and, possibly, cardiovascular disease, have been linked to PCOS. Metformin, an oral hypoglycemic agent, has been recently advocated as treatment for some women with PCOS due to the association of PCOS with hyperinsulinemia. Metformin is utilized as sole therapy for ovulation induction as well as in combination with traditional ovulation-induction therapies. This review identified 23 prospective studies addressing the effects of metformin on PCOS. Because of the heterogeneity of the published reports, only a qualitative assessment of the data was possible. Review of this literature confirms a beneficial role of metformin in reducing insulin resistance in some women with PCOS. Other favourable biochemical effects include reduced free testosterone levels and increased sex hormone-binding globulin (SHBG). Metformin may improve menstrual regularity, leading to spontaneous ovulation, and improve ovarian response to conventional ovulation-induction therapies. There is, however, little evidence supporting the use of metformin to facilitate weight reduction, or improve serum lipids or hirsutism. Further evaluation is required to define the long-term effectiveness of metformin, who will benefit from metformin treatment, and the optimal duration of metformin therapy.

Androgens↗
PubMed1988

Pulsatile GnRH therapy for the induction of ovulation in hypogonadotropic hypogonadism.

Twenty-eight patients with hypogonadotropic hypogonadism resistant to clomiphene therapy were treated with pulsatile GnRH. All the patients ovulated and there were 20 pregnancies in 16 women. Administration of the GnRH sc was successful at inducing ovulation in 19 of 22 patients whereas the treatment was successful in all of the 17 patients treated iv. There was no difference between iv and sc therapy in the rate of ovulation. Treatment was stopped after ovulation and hCG given for luteal support. The follicular phase pulse frequency was usually 90 min. In one patient ovulation only occurred with frequencies of 60 min. Higher pulse doses were usually required with sc therapy for primary amenorrhoeic patients and for those with pituitary lesions. The additional use of clomiphene increased pituitary sensitivity to GnRH resulting in ovulatory cycles in patients refractory to treatment and in ovarian hyperstimulation in a normally responsive patient. Two of the 20 pregnancies were twin--the rest were singletons. None aborted. The median time to conception was 3 ovulatory cycles. Although there were no serious complications with iv or sc therapy, the iv route is now reserved for those patients unresponsive to sc treatment as the sc route is potentially safer and more acceptable to the patient. In correctly selected patients pulsatile GnRH is a highly effective and safe new treatment for the induction of ovulation.

Adult↗
PubMed1988

Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea.

Pulsatile administration of gonadotrophin releasing hormone (GnRH) is a very effective treatment for induction of ovulation in hypothalamic amenorrhoea (HA). Thirty-seven women have been treated for a total of 117 cycles which resulted in 42 pregnancies--four treatment failures occurred. If these cycles are excluded, the 42 pregnancies were obtained within 2.3 cycles. One twin pregnancy occurred and no hyperstimulation was observed. The treatment was administered intravenously with a dosage schedule based on the grading of HA. We concluded that pulsatile GnRH was safe and very successful in induction of pregnancy in HA. Other indications (polycystic ovary syndrome and luteal phase defect) remain much less suitable for this treatment.

Amenorrhea↗
PubMed1982

Ultrasound evaluation of estrogen monitoring for induction of ovulation with menotropins.

Twenty-five cycles of induced ovulation with menotropins were investigated blindly with ultrasound to evaluate estrogen monitoring. Plasma 17 beta-estradiol (E2) and urinary estriol glucuronide (E3G) correlated with total ovarian volume (0.58, 0.58), total follicular volume (0.56, 0.52), volume of the largest follicle (0.53, 0.54), and days of administration of menotropins (0.49, 0.44), respectively. The mutual correlations of days of menotropin administration, volume of the largest follicle, E2, and E3G with total follicular volume explained the correlations of E2 and E3G with days of administration of menotropins and with volume of the largest follicle. Thus, multiple small follicles can reproduce the E2 or E3G levels associated with a single mature follicle if they result in the same total follicular volume. As menotropins were administered for progressively longer periods, the number of maturing follicles increased. We conclude that ultrasound appears to be useful for monitoring induction of ovulation with menotropins since it provides more accurate information on follicular number and size than can be obtained by estrogen determinations alone.

Chorionic Gonadotropin↗
PubMed1986

Induction of ovulation with pulsatile subcutaneous administration of human menopausal gonadotropin in anovulatory infertile women.

Pulsatile administration of human menopausal gonadotropin (hMG) via the subcutaneous route was evaluated in 15 patients with various ovulatory disorders. Administration of hMG was started at a dose of 4.6875 IU (75 IU/day) or 9.375 IU (150 IU/day) per pulse every 90 minutes. Ovulation was observed in 26 (92.9%) of 28 treatment cycles, and two singleton pregnancies were confirmed. Ovarian hyperstimulation was observed in 1 to 26 ovulatory cycles; however, no other side effects were observed during treatment. A regimen of 75 IU/day resulted in a significant increase (P less than 0.0001) of the total dose and prolongation of the treatment period for induction of ovulation, as compared with that of 150 IU/day. Shortened luteal phases occurred in ovulatory cycles induced by pulsatile subcutaneous treatment. Human chorionic gonadotropin administration given every other day until the midluteal phase significantly prolonged the duration of the luteal phase (P less than 0.05). This treatment in patients with the polycystic ovary syndrome was followed by a normalization of luteinizing hormone/follicle-stimulating hormone ratio and resulted in a successful induction of ovulation in 8 to 10 cycles. The present data demonstrated that pulsatile subcutaneous administration of hMG was effective in inducing follicular maturation and ovulation in patients with various types of anovulatory infertility.

Adult↗
PubMed1999

Early resort to ovarian stimulation improves the cost-effectiveness of a donor insemination programme.

Women undergoing donor insemination (DI) are usually regularly ovulating, therefore the role of ovulation induction in this modality of treatment has been controversial. Some recent studies reported higher pregnancy rates in stimulated cycles in comparison with natural cycles. We employed a sequential step-up protocol in which treatment was started in a natural cycle, continued with a clomiphene citrate-stimulated cycle, and finished with an ovulation induction cycle. The patients were allowed three attempts at each step before moving to the next if conception did not occur. The aim of this protocol was to enhance the cost-effectiveness of the DI programme by increasing the cycle fecundability. A total of 101 patients underwent 216 cycles of DI, including 44 patients in 80 natural cycles, 38 patients in 89 CC-stimulated cycles, and 19 patients in 47 ovulation induction cycles. The clinical pregnancy rate per started cycle (CPR/C) and per patient during this period was 14% and 30% respectively. The pregnancy rates per started cycle and per patient in the natural, CC-stimulated and ovulation induction cycles were: 13 and 32%, 10 and 18%, and 21 and 53% respectively. There was no significant difference in the CPR/C in the three groups; however, the CPR per patient in the induced ovulation cycles was significantly higher than in the CC-stimulated cycles (P = 0.005). Only one patient during this period had a multiple pregnancy in the ovulation induction group, giving an overall multiple pregnancy of 3%. By using this treatment strategy, we achieved a high clinical pregnancy rate, a low multiple pregnancy rate and a low cost of treatment per pregnancy.

Adult↗
PubMed1992

[Polycystic ovary disease: clinical picture, diagnosis and methods of therapy].

The study presents clinical features of polycystic ovaria with an incidence analysis of certain symptoms relevant for the diagnosis. Essential hormone parameters are showed, used for basal status evaluation, as well as endocrinologic tests applied for the determination of the causes of the disease within differential diagnostic investigation. Besides, in the differential diagnosis, possible diseases which should be excluded when diagnosing polycystic ovaria are showed. In the therapeutic protocol the stress is given to the methods used for the treatment of increased body hair, menstrual disorders and for ovulation induction. In the treatment of increased body hair cosmetic and medicamentous therapies are showed. In the ovulation induction method the application of clomiphene citrate, glycocorticosteroids, human menopausal genadotropins and a pulsatile pump for LHRH, have been analyzed in details. Moreover recent experiences in ovulation induction using LHRH analog (buserelin) and somatostatin analog (SMS) 201-995) are reported. Medicamentous ovulation induction was compared with surgical methods used for the induction (wedge resection and ovarial electrocauterization) pointing to the advantages and disadvantages of each method.

Diagnosis, Differential↗
PubMed1994

Pulsatile gonadotrophin-releasing hormone therapy in patients with pituitary tumours treated by surgery and irradiation.

OBJECTIVE: Pulsatile administration of GnRH for induction of ovulation is effective for women with idiopathic hypogonadotrophic hypogonadism. We were interested to assess the pituitary-ovarian response to pulsatile GnRH infusion and the therapeutic effectiveness of restoring ovulation in a group of hypogonadotrophic women previously treated with surgery and irradiation to pituitary tumours. PATIENTS: The group of patients comprised 15 hypogonadotrophic women, aged 29-40 years (mean 32.4 years), who had undergone transsphenoidal adenomectomy or craniotomy and irradiation with a total of 4500-5400 cGy in 25 fractional doses divided over 5-6 weeks. The time interval from irradiation to study was 6.3 +/- 2.0 years (mean +/- SD). TREATMENT: A single bolus GnRH (100 micrograms) test and pulsatile infusion of GnRH were performed to assess the pituitary gonadotrophin reserve and induce ovulation. We tried to correlate the pituitary response with characteristics of intracranial lesions on computerized tomography findings. We undertook ovarian biopsy in one patient who failed to respond to gonadotrophin therapy and pulsatile infusion of GnRH. RESULTS: Twelve women (80%) showed evidence of ovulation in response to pulsatile GnRH treatment and five subsequently became pregnant. Four of 12 ovulators were previous non-ovulators to exogenous gonadotrophin therapy. There was no correlation between pituitary response and character of lesions based on computerized tomography findings. A patient who failed to respond to either gonadotrophin or pulsatile infusion of GnRH had premature ovarian failure on ovarian histology. CONCLUSIONS: The functional reserve capacity of pituitary gonadotrophs may remain less impaired by tumour encroachment, pituitary surgery or irradiation than had previously been thought. This holds promise for ovulation induction in hypogonadotrophic patients who had been treated with surgery and irradiation for pituitary tumours.

Adult↗
PubMed2000

Successful pregnancy and birth after sequential cotreatment with growth hormone and gonadotropins in a woman with panhypopituitarism: a new treatment protocol.

OBJECTIVE: To report a successful pregnancy in a woman with panhypopituitarism who received 3 months of pretreatment with growth hormone (GH) before ovulation induction. Prior attempts at ovulation induction had failed for this patient. DESIGN: Case report. SETTING: Department of Endocrinology. PATIENT(S): A 32-year-old woman with panhypopituitarism and secondary infertility. INTERVENTION(S): GH (1 IU/day) alone for 3 months; during the next cycle, 1 IU/day of GH; 3 ampules of hMG per day during days 1-21; 1 ampule of hCG on day 21. GH was discontinued on day 35 when a pregnancy test was positive. MAIN OUTCOME MEASURE(S): Pregnancy and delivery. RESULTS: Pregnancy and birth of a normal child after a single ovulation stimulation using GH and gonadotropins. CONCLUSION(S): This case report suggests interest in a new protocol for follicular stimulation in women with hypopituitarism who are responding poorly to gonadotropin therapy.

Adult↗