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PubMed2003

Ovulation induction.

Anovulation, a common cause of female infertility, is a highly curable condition. Presented here is a simple treatment-orientated diagnostic scheme. Anovulatory women with low endogenous oestradiol and follicle stimulating hormone (FSH) are treated with either pulsatile gonadotrophin releasing hormone (GnRH) or gonadotropins, and women with eu-oestrogenic anovulation (mostly with polycystic ovarian syndrome; PCOS) have first-line treatment with clomiphene citrate (CC), possibly with metformin. If CC fails, FSH is administered using a chronic low-dose protocol with small incremental dose rises. A comparison of urinary with recombinant and pure FSH with luteinising hormone (LH) containing gonadotropins is made. Recombinant products are purer and more convenient for use but are expensive. LH content has little impact except in hypogonadotropic hypogonadism or severe pituitary suppression with GnRH analogues. Aromatase inhibitors, recombinant LH and long-acting FSH may find a future place in the armamentarium.

Anovulation↗
PubMed2004

Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome.

The current study was conducted to investigate the relationship between melatonin and chronic anovulation. Adult (3-4 months old) female Wistar rats were submitted to pinealectomy: group I: pinealectomized ovariectomized melatonin-treated (N = 10); group II: pinealectomized ovariectomized placebo-treated (N = 12); group III: pinealectomized light-treated placebo-treated (N = 10) or maintained under continuous light; group IV: maintained under continuous light, ovariectomized melatonin-treated (N = 22); group V: maintained under continuous light, ovariectomized placebo-treated (N = 10); group VI: maintained under continuous light placebo-treated (N = 10). In order to assess ovarian modifications, unilateral ovariectomy was performed during the fourth month in groups I, II, IV, V and the other ovary was removed after 8 months. Ovariectomy was performed in groups III and VI only after eight months. Melatonin (200 micro g/100 g body weight) dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily during the last 4 months into groups I and IV. The other groups were treated with placebo (NaCl). The ovarian cysts were analyzed and their area, perimeter and maximum diameter, as well as the thickness of the ovarian capsule were measured. Daily colpocytological smears were performed throughout the study. Persistent estrous condition and ovarian cysts were observed in all groups. In pinealectomized rats the ovarian and vaginal alterations disappeared at the end of the study and in rats maintained under continuous light the vaginal and ovarian polycystic aspect was reversed only in those treated with melatonin. We conclude that melatonin may act on the ovarian response reverting chronic anovulation induced by pinealectomy or continuous light.

Animals↗
PubMed1994

Is treatment of long-term and consecutive use of clomiphene citrate effective in anovulatory patients? Results of multi-centric retrospective studies.

The efficacy of long term consecutive treatment of clomiphene citrate (CC) was investigated in 608 infertile women associated with anovulatory disorders (classified as WHO group II amenorrhea). This study was performed in multi-centric facilities of obstetrics and gynecology by a retrospective randomized assessment. Infertile women associated with anovulation were treated by 50-150 mg of CC for five consecutive days in each treatment cycle. In this study, 200 pregnancies were observed and the total pregnancy rate was 32.9%. The number of abortions were 33 out of the 200 pregnancies (16.5%). The cumulative pregnancy rate within the pregnant subjects reached 90% in initial 10 treatment cycles and there was no difference between 50 mg and 100 mg of CC treatment. There were remarkable differences among the pregnancy rates achieved during consecutive treatments at the primary (clinics and hospital), secondary (regional center hospitals) and advanced facilities. Consecutive treatment by CC for infertile women associated with anovulation may be effective during initial 10 cycles. Although ovulation can be confirmed during the following cycles, the stimulation protocol should be reconsidered after 12 consecutive cycles therapy with CC, because cycle fecundity decreases. Hence, to improve pregnancy rates, it is important to check the previous administration of CC which reflects adversely on the subsequent conception rate especially in advanced facilities where these patients are referred to.

Anovulation↗
PubMed1999

Abnormal uterine bleeding.

The most probable etiology of abnormal uterine bleeding relates to the patient's reproductive age, as does the likelihood of serious endometrial pathology. The specific diagnostic approach depends on whether the patient is premenopausal, perimenopausal or postmenopausal. In premenopausal women with normal findings on physical examination, the most likely diagnosis is dysfunctional uterine bleeding (DUB) secondary to anovulation, and the diagnostic investigation is targeted at identifying the etiology of anovulation. In perimenopausal patients, endometrial biopsy and other methods of detecting endometrial hyperplasia or carcinoma must be considered early in the investigation. Uterine pathology, particularly endometrial carcinoma, is common in postmenopausal women with abnormal uterine bleeding. Thus, in this age group, endometrial biopsy or transvaginal ultrasonography is included in the initial investigation. Premenopausal women with DUB may respond to oral contraceptives, cyclic medroxyprogesterone therapy or cyclic clomiphene. Perimenopausal women may also be treated with low-dose oral contraceptives or medroxyprogesterone. Erratic bleeding during hormone replacement therapy in postmenopausal women with no demonstrable pathology may respond to manipulation of the hormone regimen.

Algorithms↗
PubMed1999

[Diagnosis and treatment of polycystic ovary syndrome].

Obesity, ultrasonic ovarian morphology, serum LH levels and LH/FSH ratio are inconstant symptoms of the polycystic ovary syndrome (PCOS) and are thus no longer essential for diagnosis. PCOS is diagnosed today by the finding of chronic anovulation and hyperandrogenism characterized by a high serum level of "free" testoterone. The other causes of hyperandrogenism, as well as anovulations due to hyperprolactinemia, high levels of FSH and abnormal thyroid function have to be ruled out. PCOS is very often associated with insulin resistance (IR) and hyperinsulinemia (hyper I). From in vitro and vivo studies and treatment of hyper I, it has been shown that the hyper I of PCOS stimulates androgen production. Hyper I of PCOS increases the activity of androgens: by first provoking an important decrease of the sex hormone binding globulin (SHBG) thus increasing the "free", bioactive testosterone level. and then by activating the cytochrome P 450 c 17 alpha enzymatic system that controls androgen production. Subsequent to metformin administration, the reduction of hyper I and androgen serum levels creates a favorable condition for the resumption of ovarian function and clomiphene citrate action. This explains the high percentage of ovulations and pregnancies.

Anovulation↗
PubMed2002

[Hyperinsulinemia and disorders of the menstrual cycle].

Hyperinsulinaemia and insulin resistance are usually associated phenomena of obesity and the polycystic ovary syndrome (PCO syndrome). On the other hand the PCO syndrome and obesity are often associated with disorders of the menstrual cycle and/or sterility. The authors examined 35 women aged 21 to 38 years (x = 27 +/- 4.4) with a history of anovulation cycles and/or sterility. 24 of them (68.6%) suffered from PCO syndrome. Their mean BMI was 28.95 kg/m2. 11 patients had a normal body weight, 6 were overweight and 18 were obese. The authors used the oral glucose tolerance test (oGTT) and during minute 0 and 120 blood samples were collected for assessment of the blood sugar and plasma insulin. Insulin levels in minute 0 (Io above 20 and in minute 120 (I120) above 65 uIU/ml were classified as hyperinsulinaemia. In the follicular stage of the anovulation cycle the authors assessed FSH, LH, testosterone, progesterone and prolactin. Hyperinsulinaemia ws recorded in 16 of 35 women. The mean insulin level at minute 0 was 11.9 +/- 1.3 and during minute 120 54.2 +/- 8.1 uIU/ml. The authors found significant differences in levels of I0 (6.4 +/- 1.2 vs. 16.1 +/- 1.9 uIU/ml, p < 0.01) and I120 (17.5 +/- 3 vs. 71.3 +/- 10.3 uIU/ml, p < 0.01) between obese and non-obese patients, Also in patients with the PCO there was a statistically significant difference in insulin levels of slim (BMI less than 25) as compared with obese women (BMI more than 30) (p < 0.01). A positive correlation was found between insulin levels and BMI (p < 0.01) and a liminal correlation between insulin and testosterone (p = 0.05). Patients with hyperinsulinaemia were treated with oral antidiabetics from the group of biguanides--metformin for a period of three months. During metformin treatment the insulin level declined and subsequently the menstrual cycle became normal in 11 of 16 patients with hyperinsulinaeia (68.7%), incl. two women who became pregnant. The results indicate a possible new indication of metformin in the treatment of ovarian hyperandrogenism in insulin resistant patients.

Adult↗
PubMed2004

Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines.

In the past, the diagnosis of polycystic ovary syndrome (PCOS) was based on National Institute of Health (NIH) criteria (hyperandrogenism and chronic anovulation) or on sonographic findings of polycystic ovaries. Diffe-rences in diagnosis criteria made it difficult to compare the data of studies coming from different countries. Moreover, there was criticism of both the methods used. In 2003, at a joint meeting of the European Society for Human Reproduction (ESHRE) and the American Society of Reproductive Medicine (ASRM), new guidelines for the diagnosis of PCOS were suggested. According to these guidelines, it is possible to reach a diagnosis of PCOS when at least 2 of these 3 elements are present: hyperandrogenism, chronic anovulation and polycystic ovaries. New criteria for the echographic diagnosis of polycystic ovaries have been suggested, too. These diagnostic guidelines represent important progress because they are more flexible and permit us to make the diagnosis in patients who were previously excluded by the syndrome (such as ovulatory hyperandrogenic women with polycystic ovaries or anovulatory normoandrogenic women with polycystic ovaries). However, doubts still exist and regard some borderline group of patients such as hirsute ovulatory normoandrogenic women with polycystic ovaries. A new classification of PCOS syndrome is suggested on the basis of new guidelines.

Anovulation↗
PubMed2006

Ovulatory disorders and infertility.

Ovulatory disorders represent a major cause of infertility. The World Health Organization classification offers a useful frame for diagnosis and treatment. Polycystic ovary syndrome (PCOS) is the most common cause of oligoovulation and anovulation. Treatment of infertility associated with PCOS has changed in the last decade due to the introduction of new medications. Insulin-sensitizing drugs, such as metformin, became an integral part of treatment. Aromatase inhibitors will most probably replace clomiphene citrate in the future. Women who fail to ovulate or conceive after first-line treatment options are often referred for gonadotropin treatment. Laparoscopic ovarian drilling, which has been evaluated in well-designed trials, may be an alternative to gonadotropins. In vitro fertilization, which yields high pregnancy rates, is the final treatment option when all else fails. Hypogonadotropic anovulation is treated with exogenous gonadotropins, and little has changed in its management. Women with hypergonadotropic hypogonadism should be counseled for adoption or in vitro fertilization with donated oocytes as spontaneous and treatment-associated pregnancy rates are very low.

Anovulation↗
PubMedDate not supplied

Relationship between the delayed-reaction type of LH-RH test and obesity in sterile women with ovulatory disturbances: a preliminary report.

We investigated 312 sterile women to look for a possible relationship between obesity and infertility. The LH-RH test was performed on 113 of these women. The obesity index was determined according to the Japanese variation of Broca's index. The results were as follows: (1) Among 312 sterile women, 8.7% were obese and one-fifth of anovulatory patients showed a tendency toward obesity. (2) The pregnancy rate was lower in obese women. (3) The delayed-reaction type in the LH-RH test was observed in 29.2% of total patients; the rate in patients with anovulation (20.4%) was lower than that in those with ovulation (37.3%). (4) The rate of the delayed-reaction type in anovulatory obese patients was 100%. This evidence shows that obesity was related to anovulation and/or infertility, as determined by the delayed-reaction type in the LH-RH test.

Anovulation↗
PubMed1989

Hyperprolactinemia and female infertility.

Hyperprolactinemia is a common endocrine cause of infertility in women. The pathophysiology of hyperprolactinemia in infertility is understood incompletely; however, the adverse effects of high circulating levels of prolactin on the hypothalamic-pituitary-ovarian axis cause chronic anovulation and other defects of ovarian function. Mechanisms for prolactin-induced anovulation have been postulated, and there are several contemporary approaches to the diagnosis and treatment of prolactin-secreting pituitary adenomas.

Amenorrhea↗
PubMed1989

Anovulatory infertility. Causes and cures.

Disorders of ovulation rank with tuboperitoneal disease as the most common causes of female infertility. A proper diagnosis and selection of therapy can also make anovulation the most treatable form of infertility. A review provides a framework for understanding the various etiologies of anovulation, its detection and current treatment modalities.

Anovulation↗
PubMed1977

Induction of ovulation with cyclophenyl.

The results of 495 cycles of treatment with Cyclophenyl given to 286 women suffering from amenorrhea, oligomenorrhea or persistent anovulation are reported. In 61 cases the drug solved the problems of infertility, with a success rate of 43%. The over-all success rate was 58% (288 ovulatory cycles produced in 495 treatment cycles). In detail:--in cases of prolonged amenorrhea, with plasma estradiol levels lower than 50 pg/ml, the positive results were only 15%;--in cases of short-term amenorrhea, with plasma estradiol levels lower than 50 pg/ml, the success rate was only 18%;--in cases with prolonged amenorrhea but with plasma estradiol levels higher than 50 pg/ml, the success rate was 43%;--in cases of short-term amenorrhea with plasma estradiol levels higher than 50 pg/ml, the success rate was 68%;--in cases of oligomenorrhea and of persistent anovulation, the success rate was 72%.

Amenorrhea↗
PubMed1979

Evaluating acceptance strategies for timing of postpartum contraception.

What is the best time after childbirth to accept contraception? The problem is to reduce overlap with postpartum anovulation, during which contraception is redundant, but simultaneously to reduce the proportion of women conceiving before contraception is inaugurated. Efficiencies of three classes of acceptance strategies at resolving this dilemma are investigated. Particular attention is paid to the postpartum acceptance rule because of its special administrative advantages. Its efficiency relative to those of other rules is found to be enhanced by conditions of short postpartum anovulation, a high proportion of ovulatory rather than anovulatory first menstrual cycles, a high level of natural fecundability, and, especially, a high level of contraceptive continuation.

Anovulation↗
PubMed1983

Experience with combined individualized method of hMG/hCG therapy.

The introduction of powerful ovulation induction agents, such as gonadotropins, has made an important contribution to the temporary elimination of the anovulation syndrome. Since the treatment is expensive and not without significant medical complication, it is vitally important to conduct therapy according to a well-defined monitoring system. In the past, clinicians have tended to monitor gonadotropin therapy by biophysical signs, but they were found to be insufficient monitors if used alone. Estrogen secretion from the ovaries does reflect the follicular maturation process. In this study a combined individualized method for hMG/hCG therapy is presented. Fifty-one infertile anovulatory women were treated for a total of 124 treatment cycles. All courses of therapy were judged to have induced ovulation. There was a good clinical correlation between cervical score and increasing estrogen levels. The pregnancy rate was 62.7%, with 60% of patients becoming pregnant within the first three cycles of treatment. In spite of the complications of less than 1% of severe hyperstimulation, 15.5% multiple gestation, and 28% of abortion rate, gonadotropin therapy is a most efficient tool in the treatment of infertility due to anovulation.

Adult↗
PubMed1983

Reduced pregnancy rates in AID women with unsuspected ovulatory failure.

A review over five years of 232 patients attending an artificial insemination by donor (AID) clinic was undertaken in order to detect abnormalities in ovulation patterns. Ovulation was determined by luteal phase progesterone estimations. Unexpected anovulation was found in 36% of the patients attending despite an apparently normal previous menstrual history and investigations. This group consisted of 22% who were anovulatory from commencement in the programme and 14% who became anovulatory during treatment. The cumulative pregnancy rates at 15 months for these two groups were lower (73% and 55%) than that for the remaining patients who ovulated normally (90%). A proportion (16%) of the latter group were receiving clomiphene therapy for anovulation recognized before entering the programme. The lower pregnancy rate could not be related to other factors influencing conception and occurred in spite of clomiphene therapy. These results should assist in advising patients on their chances of conception, preventing early discouragement but not encouraging long term insemination which may not improve the pregnancy rate.

Anovulation↗
PubMed1983

Amenorrhea associated with carotenemia.

Data are presented for ten women with anovulation, nine of them with amenorrhea, who have associated carotenemia. Classic explanations for carotenemia in amenorrheic patients have been weight loss or anorexia nervosa, yet carotenemia in our patients appeared to be diet induced. All patients consumed a pure or predominantly vegetarian diet; there was no intake of red meats. Clinical and laboratory data of the patients are presented. The amenorrhea of the patient is consistent with hypothalamic hypogonadotropic anovulation (HHA). It appeared that diet modification not only led to reduction in carotene levels, but also improved the menstrual status. The association of carotenemia and menstrual disorders is reviewed. The possibility that carotenemia is related to the development of HHA is discussed.

Adolescent↗
PubMed1981

[Study on hyperprolactinemic anovulatory syndrome and treatment with bromocriptine (author's transl)].

Clinical characteristic of the hyperprolactinemia were studied in 101 cases and effects of Bromocriptine were investigated in 57 cases with hyperprolactinemic anovulation. 1. Lactation was observed in 93.1% of the cases with hyperprolactinemia. There was no relationship between the degree of lactation and Prolactin (PRL) levels. 2. Hyperprolactinemia had no influence on basal gonadotropin levels. 3. In hyperprolactinemic anovulatory syndrome, a negative correlation between estradiol and PRL levels was found. PRL levels in the second grade amenorrhea were higher than those in other grade. 4. In LH-RH test, there was no relationship between PRL and LH-RH test. 5. With Bromocriptine therapy, ovulation was induced in 45 cases and pregnancy was successful in 31 cases. 15 cases of pregnancies were delivered of normal babies and 3 cases fell into abortion. 6. The initial dose of Bromocriptine was 2.5 mg/day. The dosage was increased by determining the PRL as index. 7. Cases with severe anovulation and high PRL levels, required prolonged administration. 8. 15 cases who had no ovulation by Bromocriptine administration for one month, ovulated successfully by clomiphene combined with Bromocriptine. 9. In 31 pregnant cases, there was no significant symptoms of pituitary tumor during pregnancy.

Amenorrhea↗
PubMed1995

Anovulatory infertility. The ESHRE Capri Workshop Group.

The ESHRE Capri Workshop group first arrived at a working definition of anovulatory infertility, then discussed the diagnoses, the advantages and disadvantages of the available treatments for the various categories of infertility, namely hyperprolactinaemic anovulation, hypogonadotrophic hypogonadism and normogonadotrophic anovulation including polycystic ovary syndrome.

Anovulation↗