Prevention of endometrial hyperplasia by progesterone during long-term estradiol replacement: influence of bleeding pattern and secretory changes.

OBJECTIVE: To determine the relative influences of induction of withdrawal bleedings secretory transformation, and reduction of mitosis in glands on prevention of endometrial hyperplasia during long-term hormonal replacement therapy. DESIGN: Observational expanded clinical case report. SETTING: Reproductive Endocrine Department of Hospital Necker, Paris, France, and Pathology Department of Women's Hospital, Los Angeles County and University of Southern California Medical Center, Los Angeles, California. PATIENTS: Postmenopausal women seeking treatment for symptomatic menopause. INTERVENTIONS: Endometrial biopsy and/or ambulatory hysteroscopy. MAIN OUTCOME MEASURE: Endometrial histology including progestational maturation patterns and glandular epithelial mitosis rates. Macroscopic endometrial appearance. RESULTS: The use of larger doses of E2 and P induced more marked secretory changes and more frequent withdrawal bleeding than the lower doses. There was no evidence of endometrial hyperplasia after 5 years of E2/P replacement therapy independently of bleeding pattern or progestational maturation. Consistent reduction of mitosis rates in glandular epithelium was found after 9 or more days of P administration in each cycle. CONCLUSIONS: Control of endometrial growth is mainly related to control of mitosis in glands by a relatively low doses of P. Induction of withdrawal bleeding and endometrial secretory transformation, which require larger doses of Progesterone, do not provide additional benefit for prevention of hyperplasia. Induction of amenorrhea with a relatively low dose of P may be offered to women seeking hormone replacement therapy with similar levels of safety.

Anonymous and non-anonymous oocyte donation preliminary results.

During the past year, we have developed an oocyte donation programme in 10 patients with complete absence of endogenous ovarian function (premature ovarian failure in seven cases, castration in two cases and Turner's syndrome in one case). In cases of anonymous donation, donors were volunteers devoid of any major genetical risk who were included in our IVF programme and who consented to donate one oocyte when at least seven oocytes were recovered, and two oocytes when at least 11 oocytes were recovered, to a recipient couple. As far as possible, morphological characteristics of both couples were paired. In cases of non-anonymous donation, donors were 'affective' donors, having at least one child. The resulting embryos after IVF of donated oocytes were either replaced directly in recipient women which required synchronization of the donor's and recipient's cycles, or cryopreserved and then thawed, usually at day 16 of recipient's artificial cycle, i.e. 2 days after introduction of the progestational compound. On the 10 patients entering this oocyte donation programme (20 cycles), 13 transfers were carried out resulting in four clinical pregnancies in three patients with premature ovarian failure and one with Turner's syndrome (20% pregnancy per cycle and 31% per transfer). Despite the small numbers, these good results prompted us to develop this protocol.

Results of planned in-vitro fertilization programming through the pre-administration of the oestrogen-progesterone combined pill.

The use of an oestrogen-progesterone combined pill permits the induction of ovulation in the absence of any developing follicle. Two treatments were compared. In the first, patients received no prior treatment before stimulation. In the second, combined oestrogen-progesterone treatment was given during approximately two menstrual cycles prior to stimulation. No differences between the two groups were found in relation to oocyte maturity, fertilization in vitro, cleavage, replacement and pregnancy. Fewer luteinizing hormone surges occurred in patients pre-treated with steroids. The utilization of the oestrogen-progesterone combined pill prior to induction of ovulation facilitates the forward planning of patients for in-vitro fertilization.

PIP: In order to facilitate the scheduling and management of cases for in vitro fertilization, a trial of pre-administration of a combined oral contraceptive was conducted. 103 women took 2 mg norethisterone acetate and 0.05 mg ethinyl estradiol for 45 to 70 days before induction of ovulation, allowing 5 days between treatments. This group then received either Clomid 100 mg for 6 days and HMG 225 IU on days 5, 7 and 9 (34 women), or HMG only (dose not specified, 69 women). The control groups were given identical ovulation induction regimens: Clomid and HMG (130 women) or HMG only (188 women). 70 of the patients selected for preliminary inhibition of ovulation had irregular menstrual cycles with normal prolactin; the others were picked for scheduling reasons only. No differences were documented between the groups in oocyte maturity, fertilization in vitro, cleavage, replacement and pregnancy. Pregnancy rates ranged from 10 to 16.6% in the 4 subgroups. Fewer LH surges occurred in patients pretreated with steroids. Thus the pretreatment of candidates for in vitro fertilization with ovulation blocking steroids has no quantitative effect on results, but does facilitate scheduling patients for the procedure.

Transvaginal sonographically controlled ovarian puncture for oocyte retrieval for in vitro fertilization.

Two hundred twenty-two patients took part in a trial of follicle puncture via the transvaginal route under sonographic control for the purpose of in vitro fertilization (IVF). Induction protocols were mainly human menopausal gonadotropin (hMG) + human chorionic gonadotropin (hCG) and clomiphene + hMC + hCG. In 79.7% oocyte aspiration could be achieved without difficulty via the transvaginal route. An average number of 4.7 oocytes per attempt was obtained; 10.7% evolutive pregnancies were obtained. No major incident was noted. This technique offers several crucial advantages: it reduces surgical risk, reduces the length of the patient's stay in hospital as well as the overall cost of the procedure, and it also makes possible puncture in some cases hitherto regarded as excluded.

[The value of an antiprogesterone steroid in the treatment of extra-uterine pregnancy. Preliminary results]. / Intérêt d'un stéroïde à action antiprogestérone dans le traitement de la grossesse extra-utérine. Résultats préliminaires.

The aim of this work is to study the effects of an antiprogesterone drug (RU 486) on extrauterine pregnancy and to draw from it possible inferences for therapy. The study was carried out on 28 patients presenting an extrauterine pregnancy, the levels of plasma chorionic gonadotrophins of whom were higher than or equal to 250 mIU/ml. Different modes of administration were employed and a coelioscopic salpingotomy was carried out for a pathological study.

[Tuboscopy]. / Tuboscopie.

Tuboscopy permits the observation of the tubal mucosa and the discernment of two types of lesions: synechiae and mucosal "plates". The coincidence of the interpretation of hysterography and the results of tuboscopy does not exceed 1 case in 2. Experience shows that intrauterine pregnancies which develop beyond the first trimester only survive when tuboscopy shows us a normal mucosa, whatever may be the salpingographic picture. It is better to abandon the idea of a plasty when the tubal mucosa is in a bad condition.

Endoscopy of the tube (= tuboscopy): its prognostic value for tuboplasties.

A tuboscopy was performed during tuboplasties, in 131 cases; this method gives the surgeon a direct, panoramic view of the ampullary mucosa; the lesions observed differ in 50% of cases from what was expected according to the hysterosalpingography. A 2 year follow-up shows that normal uterine pregnancies occurred only in women with at least one tube with normal mucosa according to the tuboscopy, whichever the lesions or the results of the hysterosalpingography; the other cases only had ectopic pregnancies or spontaneous abortions.