epimestrol and Infertility--Female

Female dysendocrine sterility has displayed a statistical incidence of 3.4% since 1967 in Milan's fertility and sterility centres. It is always marked by clear-cut clinical situations. Of these, particular interest is attached to anovulation (62.4% of cases), both with the cycle and with anovularity, ovarian micropolycystosis (2.7%), both as Stein ovary and as micropolycystic ovary, disturbances of ovary endocrine secretion: lutein deficiencies (21.2%) in the form of both brief and inadequate luteal phase. Treatment is aimed at possibly discontinuous reinstatement of ovulation. Clinical and pharmacological experiments over the last twenty years have put forward many "inducers". Mention is made of four personal approaches: --clinical employment of homologous gonadotropins (hMG + hCG), sequentially rather than paired, when poor gonadotropin secretion accompanied by insufficient endogenous oestrogenic activity is the main feature. Investigation from June 1964 to December 1981, coupled with monitorisation and personalisation of the treatment, initially through daily checks of total and fractionated oestrogenuria, and in recent years preferably through plasma 17-beta oestradiol or urinary enzyme determinations, has given a different slant to the reported disadvantages of gonadotropic management: hyperstimulation frequent multiple pregnancies, frequent multiple miscarriages; --employment of GnRH or its analogues (indications virtually those for paired gonadotropins). Some uncertainties however, exist with regard to the contraceptive action displayed by the agonist and antagonist analogues at certain doses, and with regard to the antigonadic action GnRH appears to have, both in the depression of oestrogen and progesterone production and in the arrest of follicular maturation an ovulation; --a preference for clomiphene among the antioestrogens in cases of primarily hypothalamic dysfunction and in ovarian micropolycystosis, provided endogenous oestrogenic activity is within normal limits; --a preference for hypoprolactinaemic drugs (bromoergocriptine, lysuride) in PRL-dependency, marked solely by an appreciable increase in serum LTH, screened as functional by means of selective tests; --experimentation of epimestrol, mainly in cases of sterility due to lutein deficiency.

Topics: Abortion, Spontaneous; Adrenal Cortex Hormones; Bromocriptine; Drug Administration Schedule; Epimestrol; Estrogen Antagonists; Female; Gonadotropins; Humans; Infertility, Female; Lisuride; Pituitary Hormone-Releasing Hormones; Pregnancy; Pregnancy, Multiple

Fifty-two women, aged from 25 to 41 years, with infertility due to chronic anovulation were admitted to the study together with 36 age-matched controls with proven ovulatory cycles. Paired plasma (3 ml) and whole unstimulated saliva (10 ml) samples were collected over a 30 day period, starting from the first day of a menstrual bleeding, in patients, and throughout the menstrual cycle, in controls. Salivary progesterone levels, measured in women with infertility, ranged from undetectable values to 16 pmol/l during the first, and from 36 to 98 pmol/l during the second half of the monitoring period. In eugonadal women the steroid levels ranged from 34 to 46 pmol/l and from 96 to 780 pmol/l during the follicular and luteal phases, respectively. The saliva/plasma progesterone ratio ranged from 0.58 to 2.71 p. cent and a good correlation between salivary and plasma levels was found at each time of monitoring. Many (86 p. cent) of patients, which were randomly allocated to a low- or high-dose epimestrol administration schedule, appeared to be sensitive to the drug, achieving, after therapy, salivary progesterone levels which were within the range of controls. Since correct assessment of luteal function in basal conditions and during therapy requires multiple steroid measurements, and since saliva can be obtained by non-invasive techniques, salivary assays represent an attractive alternative to plasma ones for monitoring ovarian activity, also during specific treatment.

Topics: Adult; Epimestrol; Female; Humans; Infertility, Female; Menstrual Cycle; Ovulation Induction; Progesterone; Radioimmunoassay; Saliva

Topics: Adult; Anovulation; Clinical Trials as Topic; Epimestrol; Estrenes; Female; Fertility Agents, Female; Follow-Up Studies; Humans; Infertility, Female; World Health Organization

Topics: Clinical Trials as Topic; Epimestrol; Female; Fertility Agents, Female; Humans; Infertility, Female; Ovary; Ovulation; Ovulation Induction; Phenobarbital; Pituitary Hormone-Releasing Hormones; Pregnancy; Stimulation, Chemical

Topics: Clomiphene; Epimestrol; Female; Humans; Infertility, Female; Luteal Phase; Medroxyprogesterone; Prognosis

Serum hCG was determined in 231 infertility patients in the late luteal phase of spontaneous and therapeutic cycles. The aim was to establish whether the discrepancy between the high number of induced ovulation cycles and the far lower cycle-related pregnancy rate can be explained by subclinical abortion. In 16.7% of spontaneous cycles hCG was positive; in 16.8% of these cases clinical pregnancy subsequently occurred. The rate of biochemically detectable pregnancies was no higher under endocrine therapy. However, under treatment with clomiphene, epimestrol, prolactin inhibitors and glucocorticoids the rate of clinical pregnancies was almost twice as high, and after hMG/hCG therapy clinically demonstrable pregnancies developed from biochemically identified ones in 76% of the cycles. The investigations show that a stimulation therapy leading to ovulatory cycles after multifollicular development increases the clinical pregnancy rate without resulting in a higher rate of very early abortions.

Topics: Bromocriptine; Chorionic Gonadotropin; Clomiphene; Embryo Implantation; Epimestrol; Female; Humans; Infertility, Female; Menstrual Cycle; Ovulation; Prednisone; Pregnancy

Topics: Adult; Epimestrol; Estradiol; Estrenes; Female; Gonadotropins, Pituitary; Humans; Infertility, Female; Progesterone

Seventeen infertile normoprolactinemic women with luteal phase defects were treated with epimestrol. In ten patients, normalization of the impaired luteal phase was achieved. Under epimestrol treatment, periovulatory estradiol concentrations (1077.3 +/- 121.5 pmoles/liter versus 612.7 +/- 64.2 pmoles/liter; mean +/- SEM; P < 0.01) and cervical scores (10.8 +/- 0.3 versus 7.9 +/- 0.38; mean +/- SEM; P < 0.01) were improved, and luteal progesterone (60.0 +/- 9.1 nmoles/liter versus 19.98 +/- 3.14 nmoles/liter; mean +/- SEM; P < 0.001) and estradiol secretioon (813.1 +/- 101.1 pmoles/liter versus 581.9 +/- 73.7 pmoles/liter; mean +/- SEM; P < 0.05) were significantly increased in those women with normalization of the luteal phase as compared with the seven patients in whom epimesterol was without effect. Prolactin levels were elevated in all patients after epimestrol therapy (P < 0.05). Basal LH levels and LH-RH stimulated levels improved following administration of epimestrol (P < 0.01) in the 10 women with normal luteal phases. FSH levels were not significantly affected. Two patients became pregnant. No side effects were noted.

Topics: Adult; Corpus Luteum; Epimestrol; Estradiol; Estrenes; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteal Phase; Luteinizing Hormone; Menstruation; Pregnancy; Progesterone; Prolactin

In a gynaecological practice 49 patients were treated for primary or secondary infertility with epimestrol between January 1977 and June 1979. The selected group all had normogonadotropic, normoprolactinaemic anovulatory cycles (group II of the WHO scientific group 1976). Therapeutic measures extended over a total of 176 cycles in which 5 mg epimestrol (1 tablet Stimovul) were prescribed from the 5th to the 14th day. This procedure led to at least one ovulation in 86% of the cases and to pregnancy in 30 of the women. 23 pregnancies were without major complications. The abortion rate was 23%. Side effects of epimestrol treatment were only seen in occasional cases and only at the beginning of treatment.

Topics: Abortion, Spontaneous; Anovulation; Epimestrol; Estrenes; Female; Germany, West; Humans; Infertility, Female; Pregnancy

The treatment of normoprolactinemic corpus-luteum deficiency with epimestrol is reported. This is a frequent cause of infertility. The clinical and hormonal parameters for the diagnosis and follow-up evaluation of the treatment are described. In the present series 10 of 17 patients with primary infertility and normoprolactinemic corpus-luteum deficiency showed a normalization of the luteal phase. Two pregnancies occured following one cycle of treatment with epimestrol at 5 mg. daily from day 3 to day 12 of the cycle. Epimestrol shows no anti-estrogenic properties in contra-distinction to other ovulation stimulating drugs. The quality of the cervical secretion is therefore not impaired by epimestrol. Side effects or ovarian cysts were not observed.

Topics: Adult; Cervix Mucus; Corpus Luteum; Epimestrol; Estrenes; Female; Humans; Infertility, Female; Ovarian Diseases; Prolactin

Topics: Epimestrol; Ergolines; Female; Humans; Infertility, Female; Pregnancy

In the course of sterility therapy 375 pregnancies were observed in 296 patients. 63 women conceived twice or more. At the first visite the mean age of the patients was 25,8 years, the mean duration of sterility 2,7 years. A primary sterility was observed in 207 and a secondary sterility in 98 cases. The main therapeutic procedure was the induction of ovulation with FSH/LH releasing preparations (Clomiphen, Cyclofenil, Epimestrol) (40,3%), followed by the substitution therapy with human gonadotrophins (22,7%). 78 pregnancies ended by spontaneous and 4 by artificially induced abortion. The abortion rate in this study was 20,8 %, exceeding considerably the normal abortion rate. The rate of extrauterine pregnancies was also increased, being 2,4%. There was no significant difference in the abortion rate of pregnancies with or without induction of ovulation. The age at the time of conception and the duration of therapy had no significant influence on the rate of abortions. In 293 pregnancies the duration of gestation exceeded the 28th week. However, 33,1% of these pregnancies had complications that required hospitalisation. Almost 50% of the complications consisted of threatened abortion. The mean duration of gestation was reduced by 5 days, caused by a relatively high frequency of early births (16,9%). The mode of delivery of our patients was in 68,8% spontaneous delivery, in 16,2% caesarian section, in 15,0% forceps or vacuum extractions. This corresponds to the general mode of delivery of our hospital. Only after gonadotrophin therapy a higher caesarian section rate of 26,8% was noted. Out of the 310 live born children, 9,2% had a weight below 2500 g, owing to a multiple pregnancy rate of 4,1%. 4% of the children showed the signs of dystrophia. The perinatal mortality amounted to 5,1%. However, when the gonadotrophin induced multiple pregnancies are excluded, the rate is 2,7%. Only 2 cases of malformations were observed.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Epimestrol; Evaluation Studies as Topic; Female; Humans; Infant, Newborn; Infertility, Female; Menotropins; Pregnancy

Ovulation induction has been used regularly in our department for several years to treat functional sterility. 4. various preparations and methods have been applied. The success rate is 31.3%. Altogether there have been 400 pregnancies, 274 of them have come to term, 126 patients are still pregnant. In 50% of the cases the pregnancy was uncomplicated and in 48.7% labour was normal. The number of abortions and premature labour is high and the prophylactic gestagene therapy has been successful in protecting the pregnancy. There have been more pathologies during labour, so the frequency of interventions is higher. The perinatal mortality of the mature newborn is 2.3%, but the perinatal mortality in premature labour is very high (14.7%). The total perinatal loss is 9.8%. The frequency of malformations is not higher as was previously suspected.

Topics: Abortion, Spontaneous; Cesarean Section; Clomiphene; Epimestrol; Female; Fetal Death; Gonadotropins; Humans; Infertility, Female; Obstetric Labor Complications; Ovulation Induction; Pregnancy; Risk

155 patients have been treated with epimestrol during 593 menstrual cycles in a daily dosage of 5, 10 or 2.5 mg from the 1st to the 10th or from the 5th to the 14th day of the cycle. 143 patients with secondary amenorrhoea, anovulatory cycles, ovulatory oligomenorrhoea, corpus luteum insufficiency, and normal cycles received epimestrol after an average period of 2.4 years of involuntary infertility. The pregnancy rate was 21% (n = 30), the spontaneous abortion rate 13% (n = 4). Twelve further patients not seeking pregnancy were treated with epimestrol because of secondary amenorrhoea and (or) anovulatory bleeding. The results were as follows: 1) In eugonadotropic secondary amenorrhoea 8 out of 12 patients ovulated, 5 out of 10 patients wanting children became pregnant. No patient with hypogonadotropism ovulated. 2) Out of 25 patients with anovulatory cycles or bleeding 13 ovulated and 4 became pregnant. 3) 17 out of 68 oligomenorrhoeic patients became pregnant. 4) In 12 out of 24 patients with corpus luteum insufficiency the hyperthermic phase improved and four patients became pregnant. 5) In 12 patients without anomalous cycles these remained unchanged and there were no pregnancies. 6) No side effects could be observed.. 155 women (593 cycles) were treated for sterility with daily doses of 5, 10, or 2.5 mg of epimestrol, from the 1st to the 10th or from the 5th to the 14th day of the cycle. 143 of these patients suffered from secondary amenorrhea, anovulatory cycles, ovulatory oligomenorrhea, corpus luteal insufficiency, and even normal cycles, which resulted in an average of 2.4 years of involuntary sterility. The pregnancy rate was 21% (n = 30) and the rate of spontaneous abortion 13% (n = 4). 12 other women were treated with epimestrol because of secondary amenorrhea or anovulatory bleeding. In those patients with eugonadotropic secondary amenorrhea, 8 of 12 ovulated and 5 of 10 desiring children became pregnant. No patients with hypogonadotropism ovulated. Of 25 patients with anovulatory cycles or bleeding, 13 ovulated and 4 became pregnant. Of those with oligomenorrhea, 17 out of 68 became pregnant. 12 out of 24 patients with corpus luteal insufficiency showed in improvement in the hyperthermic phase and 4 became pregnant. 12 patients with normal cycles showed no change and did not become pregnant. No side effects were experienced.

Topics: Abortion, Spontaneous; Amenorrhea; Anovulation; Berlin; Epimestrol; Estrenes; Female; Humans; Infertility, Female; Oligomenorrhea; Pregnancy; Time Factors

In 24 women with disturbances of ovulation treated for sterility with Epimestrol, ovulation was achieved in 3 patients but none of these became pregnant after therapy. Since it has been suggested that the association of Clomiphene with a weak estrogen might improve the pregnancy rate, we decided to administer Clomiphene associated with Epimestrol. Using this combined therapy in 58 patients, 32 out of the 58 women ovulated and 17 conceived. The overall rate of pregnancy using the combined therapy was no better than that obtained when Clomiphene alone is administered. From this study it is concluded that: (1) Epimestrol is not an effective method for the induction of ovulation, and (2) addition of Epimestrol to Clomiphene is of no clinical benefit.

Topics: Clomiphene; Drug Evaluation; Drug Therapy, Combination; Epimestrol; Estradiol; Estrenes; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Luteinizing Hormone; Ovulation

Epimestrol 5 mg. daily for 10 days was administered in 119 treatment cycles to 21 women with normal gonadotropins and 33 ovulations were induced. Of the 21 patients, 7 had secondary amenorrhea, 10 had anovulatory oligomenorrhea and 4 had ovulatory oligomenorrhea. 17 patients desired pregnancies and 6 became pregnant. There was 1 pregnancy among 5 women with secondary amenorrhea. There were 3 pregnancies among 9 patients with anovulatory oligomenorrhea and 2 pregnancies in 3 patients with ovulatory oligomenorrhea. The pregnancy rate was 35%. Side effects were not observed.

Topics: Adult; Amenorrhea; Epimestrol; Estrenes; Female; Humans; Infertility, Female; Infertility, Male; Male; Oligomenorrhea; Ovulation; Pregnancy

Topics: Adult; Clomiphene; Cyclofenil; Epimestrol; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Menotropins; Ovary; Ovulation; Pregnenediones; Stimulation, Chemical