Comparison of luteal phase profile in gonadotrophin stimulated cycles with or without a gonadotrophin-releasing hormone antagonist.

BACKGROUND: The aim of our study was to explore luteal phase hormone profiles in gonadotrophin-stimulated cycles with or without gonadotrophin-releasing hormone (GnRH) antagonist therapy during intrauterine insemination (IUI). Forty-one infertile couples were recruited in this randomized clinical study. METHODS: The 19 patients included in group A were treated for 21 cycles with recombinant FSH 150 IU/day starting from day 3 of the cycle and with the GnRH antagonist cetrorelix at the dose of 0.25 mg/day starting from the day in which a follicle with a mean diameter of > or =14 mm was seen at ultrasound scan. Cetrorelix was administered until human chorionic gonadotrophin (HCG) administration. The 22 patients included in group B were administered recombinant FSH alone at the same dosage for 27 cycles. RESULTS: The two treatment groups showed a similar increase in progesterone concentration during the luteal phase. In the mid-luteal phase (day 6 after HCG), oestradiol concentrations in group B were significantly higher compared with group A (P < 0.05) but the oestradiol:progesterone ratio was similar in the two groups. Serum LH was completely suppressed during the follicular phase only in group A, concomitantly with GnRH antagonist administration. A total of six pregnancies, all ongoing, were achieved (14.3% per patient and 12.2% per cycle), equally distributed in group A and in group B. CONCLUSION: GnRH antagonists can be safely administered in gonadotrophin-stimulated IUI cycles without luteal phase supplementation because no deleterious effects of GnRH antagonist administration were noted on luteal progesterone concentration or on the duration of the luteal phase.

Anthropometric indicators and response to gonadotrophin for ovulation induction.

A total of 111 women with no ultrasonographic findings of polycystic ovarian syndrome were observed between January 1989 and December 1991 in an in-vitro fertilization (IVF) programme. The treatment schedule involved ovulation induction after treatment with a gonadotrophin-releasing hormone (GnRH) agonist, using standard doses of human menopausal gonadotrophin (HMG) for 4 days, and further stepwise increments in dosage as required. Response to the treatment was defined as: (i) presence/absence of one or more follicles > or = 10 mm diameter after 4 days of treatment, and (ii) oocyte retrieval. Three indices of body mass were considered: weight (W) in kg/height (H)2 in metres (Quetelet's index), W/H1.5 (the National Health and Nutrition Examination Survey anthropometric index for women), W0.30/H (ponderal index). Surface area was computed as 0.0235 (H in cm0.422) (W in kg0.515). Women in the upper tertiles of the range of anthropometric indicators more frequently tended to present no follicle > or = 10 mm on day 7. Likewise, oocytes were retrieved less frequently in subjects in the higher tertile than in those in the lower. The odds ratio of a negative response both on day 7 and at the end of treatment increased with the tertiles of body mass indices or surface areas. This study suggests that response to ovulation induction treatment is inversely related to body mass index.

Lack of immunization after intraperitoneal insemination of spermatozoa.

Twenty infertile patients with normal tubal patency were inseminated intraperitoneally (11 once, seven twice, and two three times) with spermatozoa (mean 14 x 10(6), range 0.6-48 x 10(6)) prepared by the standard swim-up technique. The occurrence of immunization to spermatozoa was looked for by the Gelatin Agglutination Test (GAT) and Tray Agglutination Test (TAT). Both tests gave negative results for all the controls (10 pregnant and 10 puerperal women). Antisperm antibodies were measured in the serum before, 30 d and 4-7 months after Intraperitoneal Insemination (IPI). The last check was done for only 14 patients, since six became pregnant as a consequence of the first treatment. Of the 14 patients studied after 4-7 months, seven had two, and two had three IPI. In the group of inseminated patients, 18 women with no basal sperm antibody did not show evidence of antibody formation after the treatment and it was not increased after insemination in the two patients who already had low antibody titre (1/32). In conclusion, despite the large number of spermatozoa inseminated and even after several IPI attempts, there was no evidence of de novo production of or increase in already present anti-sperm antibodies according to the methods used for the detection of ASA in this study.

Echoguided transvaginal oocyte retrieval: effective and easy to learn technique.

Echoguided transvaginal oocyte retrieval gives good results even when carried out after a short training course. This study compares the results obtained by a group of physicians with long experience and a newly-trained group. No significant differences were found in the percentages of follicles punctured (87.9% vs 91.9%), of oocytes recovered (62.8 vs 70.6%), in the mean number of follicles aspirated (4.5 vs 4.1) or in duration of the procedure (33.9 min vs 34.2 min). No complications occurred in the retrieval and the patients, pain was very slight.

Pregnancy after direct intraperitoneal insemination of spermatozoa from a man with severe infertility, after unsuccessful application of other methods of assisted fertilization.

Direct intraperitoneal insemination (DIPI) is one of the least invasive strategies of assisted reproduction. Unexplained infertility and male sub-fertility are the major indications for DIPI. It is otherwise well known that assisted procreation gives poor results in severe male infertility. This is a report of a pregnancy that occurred as a result of a direct intraperitoneal insemination of prepared spermatozoa characterized by a particularly severe astheno-teratozoospermia in a couple unsuccessfully treated with other, more invasive methods of assisted fertilization.

Pregnancy after intraperitoneal insemination during a natural cycle.

The success rate after intraperitoneal insemination is also imputed to superovulation protocols. We report here the first case, to our knowledge, of pregnancy following intraperitoneal insemination during a natural cycle.

IVF: induction of ovulation in poor responders.

All IVF programs have a consistent rate of failure in inducing ovulations. Pharmacological induction of ovulation is otherwise crucial for an IVF program because of the need for more than one ovum. Since it is well known that the best candidates for HMG treatment are hypogonadotropic women a short reversible hypogonadotropic state was induced in IVF patients by LH-RH agonist (Buserelin). Superovulation was then achieved with very high initial doses of FSH (Metrodin) in order to maximize the ovarian response. This technique used in 116 IVF women induced a satisfactory follicle growth even in 70% of the patients already poorly responsive to HMG stimulation.

Ovarian stimulation of IVF patients: effects of the reversible hypogonadotrophic state induced by GnRH agonist.

Multiple ovulation was induced in 122 hypogonadotrophic IVF patients with large doses of HMG. The hypogonadotrophic state, short and reversible, was obtained by nasal administration of a GnRH agonist (200 micrograms, five times per day). In the 97 induced cycles, a mean of 9.1 follicles was recorded. A comparison of the results obtained for 36 patients who had already been treated with clomiphene and HMG showed both significantly more follicles per cycle (8.5 versus 3.0) and an increase in oocytes retrieved (6.7 versus 1.3) when treated with the agonist and HMG. In addition 11 of 18 already poorly responsive patients had normal responses. The luteal phase was supported by either HCG or progesterone injection. Plasma progesterone profiles were satisfactory and, as expected, the highest progesterone concentrations were associated with HCG treatment.

Hysteroscopy versus hysterosalpingography in infertile patients.

The purpose of this study is to compare the results of Hysterosalpingography (HSG) and those of Hysteroscopy (H) in order to evaluate intrauterine morphology in a sample of 47 infertile patients. In the HSG sample having no intrauterine pathology, H showed up a pathological condition in 30% of the cases. Similarly, in the cases in which HSG showed pathologies, H gave normal results in 33.3%. Considering H to be a simple diagnostic method, which causes little trauma to the patient, and is more precise than HSG, the authors recommend the hysteroscopic approach, especially in cases of sterility of unknown origin.

Preparation of a partially desialylated human chorionic gonadotrophin (hCG) and its use for induction of ovulation after ovarian stimulation with human menopausal gonadotrophin.

A method for the large scale preparation of partially desialylated human chorionic gonadotrophin suitable for human use is reported. To obtain the desired grade of desialylation and to avoid the presence of the enzyme in the modified hormone, neuraminidase coupled to Sepharose 4B was used. The preparation showed to be active in vitro (OAAD and SVW tests) and its half-life was found to be 13 min in the rat and 75 min in human beings. This desialo hCG proved to be effective in inducing ovulation in amenorrhoeic women. Among 39 induced cycles 31 ovulations and 5 pregnancies occurred.

Study of a new intrauterine device, the multiload 250 CU.

The multiload 250 CU intrauterine device has been inserted in 298 women. Its effectiveness and the side effects connected with the use have been studied for a total of 3455 months of use. Two pregnancies and 5 expulsions have been observed while twelve devices were removed for pain and bleeding. The data compares quite favourably with those obtained with other IUDs.

Effect of three serotonin antagonists on plasma prolactin response to suckling in puerperal women.

The effect of the acute administration of three serotonin antagonists on plasma PRL levels and on the PRL response to suckling was investigated in a group of puerperal women. A single oral dose of metergoline or methysergide induced a significant decrease of plasma PRL levels and abolished the PRL response to suckling. Cyproheptadine administration did not modify either the plasma PRL levels or the PRL response to suckling. These results are discussed in light of the known pharmacological properties of the three antiserotonergic drugs.

Antiserotonin treatment of hyperprolactinemic amenorrhea: long-term follow-up with metergoline, methysergide, and cyproheptadine.

Twenty patients affected by hyperprolactinemic amenorrhea-galactorrhea have been treated with one or more of the following serotonin antagonists: metergoline, methysergide, and cyproheptadine. Among the 11 patients without evidence of pituitary tumor resumption of menses was observed in five, two of whom had ovulatory cycles; one patient became pregnant; ovulations occurred only during treatment with metergoline. In the group of nine patients with enlarged sellae, three experienced isolated episodes of bleeding, while two had three and four menses each, respectively; all cycles were anovulatory. Plasma prolactin levels and galactorrhea were favorably affected by treatment only in a minority of amenorrhea-galactorrhea patients with and without tumors.

Comparison of placebo and bromocriptine in the treatment of patients with normoprolactinaemic amenorrhoea.

Fourteen women with normoprolactinaemic amenorrhoea were treated with bromocriptine (2.5 mg twice daily) for a period ranging from 4 to 17 weeks, while a matched group fo 19 amenorrhoeic women were treated with a placebo (one tablet twice daily) for 4 to 12 weeks. About half of the patients in both groups had at least one episode of vaginal bleeding during treatment. There was no clear difference in the menstrual and ovulatory pattern between placebo and bromocriptine groups.

Suppression of puerperal lactation by metergoline.

Based on the known stimulatory effect of serotonin on prolactin secretion, a trial of suppression of puerperal lactation by a potent serotonin antagonist, metergoline, was carried out in 30 puerperal women who did not want to nurse. The drug was administered orally at the dose of 4 mg tid for 5 days to all subjects, starting between 24 and 72 hours from delivery. Lactation was either prevented or rapidly suppressed in all subjects. Rebound of lactation after the end of treatment was observed in 10% of cases. Metergoline administration was associated with a significant suppression of the plasma prolactin levels.

Failure of dopamine infusion to suppress the plasma prolactin response to sulpiride in normal and hyperprolactinemic subjects.

In eleven normal women dopamine infusion (5 microgram/Kg/min) significantly lowered plasma prolactin levels but failed to suppress the PRL response to sulpiride (10 or 100 mg i.v.), while the same dose of dopamine was effective in abolishing the PRL response to TRH (200 microgram i.v.). In four hyperprolactinemic women showing an impaired PRL response to sulpiride, dopamine infusion was effective both in lowering PRL circulating levels and in restoring an evident response to sulpiride. This finding suggests an impairment of endogenous dopamine activity in hyperprolactinemic amenorrhea.

Pregnancy following metergoline treatment in a patient with hyperprolactinaemia.

A 33-year-old woman who had had amenorrhoea and galactorrhoea for ten years and had hyperprolactinaemia was treated with metergoline, a serotonin antagonist. There was a marked decrease in plasma prolactin levels. After two months, ovulation and pregnancy occurred. This is the first such report.

PIP: A case study of a 33-year-old hyperprolactinemic woman becoming pregnant after treatment with metergoline is reported. The patient had also had amenorrhea and galactorrhea for 10 years. Treatment twice a day with 4 mg metergoline, a serotonin antagonist, markedly decreased plasma prolactin levels. 2 months later the patient became pregnant and delivered a normal, healthy boy. This is the 1st report of ovulation induction by metergoline.