Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinyl estradiol on the human endometrium.

OBJECTIVE: To provide an in-depth assessment of the effects of the combined oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (Yasmin, Schering AG, Berlin) on the endometrium by means of endometrial morphometry in comparison to an untreated cycle. DESIGN: The open, multicenter study consisted of one untreated precycle and 13 treatment cycles. SETTING: Four gynecologic clinics in Belgium, The Netherlands, and Switzerland were involved. PATIENT(S): Forty women with a history of regular menstrual cycles. INTERVENTION(S): Before the commencement of the trial, 3 months without any hormonal intake was obligatory. The first endometrial sample was done in the untreated precycle, adjusted to the day of LH peak plus 5 to 6 days. During the medication phase, endometrial samples were taken at cycle 3, 6 and 13. MAIN OUTCOME MEASURE(S): Primary outcome measure of the study was the morphologic assessment of the endometrium with measures such as glandular diameter, glandular epithelial height, and number of vacuolated cells per 1,000 glandular cells. Furthermore, the endometrial thickness was measured by ultrasound. RESULT(S): After 13 cycles of medication use the endometrium had an atrophic appearance in 63% of the subjects. The size of the glands, the glandular epithelial height, and the number of glands per square millimeter were already significantly reduced after 3 months' use. Histological and ultrasonographical evaluation of the endometrium indicated a suppression of the proliferative activity of the endometrium. CONCLUSION(S): The combination of 30 microg of ethinyl estradiol with 3 mg of drospirenone induces changes of the endometrium that are comparable with other combined oral contraceptives and exhibits a marked antiproliferative effect on the endometrium. The medication was proven to be an effective oral contraceptive and revealed good cycle control characteristics.

Endometrial evaluation is not predictive for in vitro fertilization treatment.

PURPOSE: The main purpose of this study was to evaluate ovarian function by clomiphene citrate (CC) challenge test in a group of tubal infertile women and to study endometrial morphological maturation in the early luteal phase of CC-stimulated cycles as compared to in vitro fertilization (IVF) treatment outcome. METHODS AND RESULTS: Four women presented with strongly retarded, proliferative endometrium in the luteal phase. Of these, three presented with impaired ovarian function, high basal follicle-stimulating hormone, and high follicle-stimulating hormone levels after clomiphene stimulation on cycle day 10. In the remaining 30 women, showing an in-phase endometrium after CC stimulation, a comparison of six morphological characteristics did not reveal any significant differences between the 14 women who did become pregnant and the 16 who did not. No significant differences in endometrial thickness were observed between the groups. Significant differences were found when comparing estradiol and progesterone area under the curve during the luteal phase (P < 0.001 and P < 0.01, respectively) between those who did and those who did not become pregnant. CONCLUSIONS: Luteal endometrium morphology was not a sharp instrument to detect differences between women who did and women who did not become pregnant following IVF treatment, while ovarian function, as measured by hormonal markers, seemed to be a more reliable prognostic factor for IVF treatment outcome.

Importance of endometrial quality in women with tubal infertility during a natural menstrual cycle for the outcome of IVF treatment.

PURPOSE: The importance of endometrial maturation at estimated time of implantation for the outcome of IVF treatment in regularly menstruating women with tubal infertility was evaluated. METHODS: FSH was measured on cycle day 3, on days 10-15 urine and blood were collected to estimate the day of the LH peak, and E2 and P4 were measured during the luteal phase, on cycle days 19-26. An endometrial biopsy was obtained on days LH + 3 to LH + 6. RESULTS: The number of subjects with delayed endometrial maturation was larger in the group of infertile women who did not become pregnant compared to pregnant women and controls. Those infertile women who did not become pregnant after IVF treatment also presented with a higher basal FSH on cycle day 3 and lower E2 and P4 AUC in the luteal phase. Six infertile women and two controls presented with mid- and late-proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in the presence of adequate E2 and P4 secretion. Six morphological characteristics were compared in the three groups: (1) 17 infertile women who became pregnant, (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile women did not differ from the controls. The numbers of glandular and stromal mitoses were significantly higher in those women who did not become pregnant (P < 0.01) compared with those who became pregnant. Endometrial biopsies obtained on cycle days LH + 5 and LH + 6 showed significant differences in glandular epithelial height (P < 0.05) and number of vacuolated cells among the nonpregnant women (P < 0.01), the pregnant women (P < 0.05), and controls. CONCLUSIONS: A higher frequency of retarded endometrial development in women who did not become pregnant following IVF treatment was found. In some cases, endometrial insensitivity could most likely cause retarded endometrial development and failure of implantation after IVF treatment, which could not be overcome by routine luteal-phase support. However, our results do not allow conclusions concerning its relative importance compared to preembryo quality; this has to be investigated further.

Effect of low daily doses of mifepristone on ovarian function and endometrial development.

The effects of low daily doses of the antiprogestin mifepristone (RU 486) on ovarian and endometrial function were studied. The study included one control cycle, three treatment cycles and one follow-up cycle. During the treatment cycles, either 0.1 (n = 5) or 0.5 (n = 5) mg of mifepristone was administered once daily. Urine samples were collected three times weekly during the control and treatment cycles and pregnanediol glucuronide and oestrone glucuronide and luteinizing hormone (LH) were quantified by radioimmunoassay. Blood samples for cortisol measurement were collected once weekly and for serum glycodelin at the onset of menstruation. An endometrial biopsy was obtained in the mid-luteal phase in the control cycle and in the first and third treatment cycles and analysed by morphometric and histochemical methods. Binding of Dolichus biflorus agglutinin (DBA) lectin was measured and expression of progesterone and oestrogen receptors and glycodelin were analysed immunohistochemically. All cycles studied were ovulatory with an LH peak and elevated pregnanediol glucuronide concentrations. Follicular development seemed normal as judged by ultrasound examination. The length of the menstrual cycle and the menstrual bleeding were not significantly altered. Following administration of 0.5 mg mifepristone/day, endometrial development appeared to be slightly retarded and glandular diameter was significantly reduced. Furthermore, significant decreases in DBA lectin binding and endometrial expression of glycodelin were observed. Daily doses of 0.1 mg did not have any significant effect on the endometrium. No differences in oestrogen or progesterone receptor immunoactivity between control and treatment cycles were seen. This study provides further evidence that endometrial function is sensitive even to doses of antiprogestin that are low enough not to disturb ovulation. It remains to be established whether these effects are sufficient to prevent implantation.

Transdermal sequential and continuous hormone replacement regimens with estradiol and norethisterone acetate in postmenopausal women: effects on the endometrium.

OBJECTIVE: To evaluate, in postmenopausal women, the endometrial safety and histologic effects of two doses of transdermal norethisterone acetate (NETA) administered in sequential and continuous treatment regimens added to continuous transdermal estradiol, against a reference regimen consisting of sequential oral progestogen and continuous transdermal estradiol. METHODS: A total of 774 postmenopausal women were enrolled in the open-label study of 13 treatment cycles of 28 days each and randomly assigned evenly to regimens consisting of transdermal estradiol, 50 micrograms/day and NETA, given sequentially (last 14 days of each treatment cycle) or continuously at two doses (170 and 350 micrograms/day). Estradiol and NETA were delivered from a transdermal system containing both hormones. The reference group received estradiol, 50 micrograms/day transdermally and either 1 mg/day NET or 20 mg/day dydrogesterone orally during the last 14 days of each treatment cycle. Endometrial biopsies were taken pre-study and at the end of the treatment, if treatment had lasted at least 3 months. Safety was to be assessed in terms of the incidence of hyperplasia. Endometrial biopsies were assigned to one of the following histological classes: proliferative (predominant estrogen effect), suppressed proliferation (slightly, moderately, strongly progestogenic effect), progestational atrophy (predominant progestogenic effect), hyperplastic, cancerous, or other. RESULTS: No case of hyperplasia was recorded in any of the treatment groups, each with > 150 subjects enrolled, after one year of treatment. One case of serous carcinoma was found in the LP-C group. Progestational atrophy was seen frequently in women receiving continuous transdermal HRT (84%, high-dose NETA, 66%, low-dose NETA); it was much rarer with the sequential regimens (i.e., between 32% and 38%). The proportion of estrogen-dominated endometria was low, 0.9% and 2.6% with the high- and low-dose NETA continuous regimens, respectively, 6.2% and 12.5% with the high- and low-dose NETA sequential regimens, respectively; and, 4.5% in the oral progestogen group. CONCLUSION: Transdermal administration of either dose of NETA, whether given sequentially or continuously, prevents the emergence of hyperplasia expected with unopposed estradiol. Since differences in outcomes of endometrial histology between the two NETA doses were minor for both continuous and sequential regimens, use of the lower NETA dose is considered sufficient for a safe transdermal combination hormone replacement therapy.

Effect of post-coital contraceptive methods on the endometrium and the menstrual cycle.

STUDY OBJECTIVE: To evaluate the effect of treatment with ethinylesteradiol-levonorgestrel or danazol on ovarian function, gonadotrophin release and endometrial development during the time when a pregnancy may occur following unprotected intercourse. METHODS: Women with regular menstrual cycles were followed during one control, one treatment and one follow-up month. The women obtained either a combination of 0.5 mg levonorgestrel and 0.1 mg ethinylestradiol (Yuzpe regimen: n = 16) or 600 mg danazol orally and repeated after 12 hours (n = 16). The treatment was administered on either cycle day (cd) 12 or day LH +2. An endometrial biopsy was obtained once on cd LH +6 to +8 in the subjects treated on cd LH +2 both in control and treatment cycles, and morphometric analysis was performed. The concentrations of LH, pregnandiol (P2G), and estrone (EIG) glucuronide were followed daily in morning urine during control and treatment cycles. RESULTS: Following treatment with the Yuzpe regimen on cd 12 the LH surge was either undetectable (three subjects), postponed to cd 16 to 22 (three subjects) or cd 38 to 39 (two subjects) with lower P2G and LH levels than in the control cycle. Following preovulatory treatment with danazol, no LH peak could be detected in four subjects and in the remaining four subjects the LH peak varied between cd 13 and cd 24. The mean area under the curve for LH was significantly lower, the levels of EIG were slightly higher and the P2G levels were unaffected in comparison with the control cycle. Neither of the two treatments administered on cd LH +2 affected the hormonal pattern and only a discreet effect on the development of the endometrium was seen after the EE/LNG treatment. CONCLUSION: The findings indicate that the contraceptive effect of postcoital treatment with EE/LNG and danazol is mainly due to an inhibition or delay of ovulation and insufficient corpus luteum function. The direct effect on the endometrium is limited, if any.

Analysis of the karyotype and desoxyribonucleic acid content of uterine myomas in premenopausal, menopausal, and gonadotropin-releasing hormone agonist-treated females.

OBJECTIVE: To correlate the cytogenetics and the DNA content in uterine myomas. DESIGN: Prospective study in treated and untreated females. SETTING: Tertiary University Center. PATIENTS: Premenopausal, menopausal, and GnRH-agonist (GnRH-a)-treated patients. INTERVENTION: Myomectomy or hysterectomy. MAIN OUTCOME MEASURE: Karyotype analysis and the DNA content measured by microfluorescence technique and expressed in fluorescence units. RESULTS: The mean DNA content in cells from karyotypically normal and karyotypically abnormal myomas, respectively, was 37.4 +/- 6.9 and 30.4 +/- 1.8 fluorescence units in premenopausal females, 30.3 +/- 5.3 and 28.7 +/- 0.9 fluorescence units in menopausal females, and 31.6 +/- 2.7 and 32.9 +/- 5.8 fluorescence units in GnRH-a-treated females. CONCLUSIONS: Forty percent of the myomas evaluated demonstrated an abnormal karyotype and had a significantly lower DNA content than the chromosomally normal myomas. After GnRH-agonist treatment, the DNA content was decreased in the euploid myoma group only.

A new method to study the process of implantation of a human blastocyst in vitro.

OBJECTIVES: To develop a "miniorgan" culture of human endometrium dated according to the LH peak in order to study the process of implantation of a human blastocyst in vitro. DESIGN: Preliminary results of a more extensive study with the same objectives. SETTING: Hospital-based unit of reproductive health and university-related reproductive research laboratories. PATIENTS: Six apparently healthy women with normal regular menstrual cycles providing endometrial material 4, 5 and 6 days after the LH peak. INTERVENTION: One part of the biopsy was used for histologic dating. The other part was incubated in culture medium RPMI-1640 and exposed to the contact with one to three embryos fertilized in vitro. MAIN OUTCOME MEASURE: Biopsy material before and after incubation was studied by morphometric methods in a light microscope. The histologic changes were recorded by photomicrographs. RESULTS: Implantation of an embryo obtained 4 days after IVF penetrated the lining endometrial epithelium of a biopsy obtained 4 days after the LH peak and kept in vitro for 24 hours. The embryo was placed on the lining epithelium of the endometrium within 3 hours after the biopsy was taken. CONCLUSION: A new method to study the process of implantation of a human embryo in vitro has been described, allowing the embryo to penetrate the lining endometrial epithelium in a biopsy obtained at LH +4/+5.

Effects of clomiphene citrate stimulation on endometrial structure in infertile women.

Investigations into the effect of clomiphene citrate stimulation on endometrial differentiation were retrospectively performed in the mid-luteal phase on 21 patients undergoing ovulation induction prior to artificial insemination. A high incidence of irregular endometrial development was seen using morphological and morphometric criteria; in addition, increasing stromal oedema after clomiphene citrate treatment was observed. Measurable differences in glandular development (i.e. numbers of glands and glandular epithelial height) were found in early luteal phase biopsies (LH+2/+6) from patients treated with clomiphene citrate and normal fertile controls. Impaired endometrial development in the early luteal phase, which is a sensitive interval in preparation for implantation, might lead to an effective asynchrony between embryonic and uterine development and unfavourably influence the outcome of implantation.

Effect of low weekly doses of mifepristone on ovarian function and endometrial development.

The effect of a low dose of mifepristone (RU486) on ovarian and endometrial function was studied in 14 healthy women. The study included one control and two treatment cycles. During the treatment cycles, either 2.5 mg (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly. The concentration of ovarian steroids and luteinizing hormone (LH) in urine was measured daily, cortisol in blood once weekly and glycodelin (placental protein 14; PP14) at the time of menstruation. Ovarian function was monitored by vaginal ultrasound. An endometrial biopsy was taken in each cycle in the mid-luteal phase, based on self-measurement of the LH peak, or on cycle day 22 if no LH peak could be detected. In the evaluation of the results, the outcome of the enzyme immunoassay of LH was used to date the biopsy. Endometrial progesterone and oestrogen receptors and Dolichus biflorus agglutinin (DBA) lectin binding were measured. Ovulation was not inhibited by treatment with mifepristone, and an LH peak could be determined in all control and treatment cycles. However, in four subjects (one with the higher and three with the lower dose) the follicular phase was prolonged by 6-13 days. The duration of the luteal phase and the concentrations of pregnanediol and oestrone glucuronide were not affected by treatment. A dose of 5 mg, and to a lesser extent 2.5 mg, mifepristone once weekly caused desynchronization of endometrial development. Endometrial progesterone receptor, but not oestrogen receptor, concentration was significantly increased by the higher dose. A significant reduction in DBA-lectin binding and in serum glycodelin concentrations was also found. Thus, low doses of mifepristone do not inhibit ovulation but delay endometrial development and impair secretory activity. Whether these effects are sufficient to prevent implantation remains to be established.

Effects of a single post-ovulatory dose of RU486 on endometrial maturation in the implantation phase.

The effect of a single post-ovulatory dose of RU486 on endometrial maturation was studied in the implantation phase. A total of 11 healthy women were followed for one control and one or two treatment cycles. In treatment cycles, a dose of 200 or 400 mg RU486 was administered on day luteinizing hormone (LH)+2. In both control and treatment cycles, an endometrial biopsy was obtained on LH+6 to LH+8. These biopsies were assessed by morphometric and immunohistochemical analyses. The treatment with RU486 did not disturb the normal menstrual rhythm but caused a significant inhibition in the endometrial development. Glandular progesterone receptor staining was significantly more pronounced after RU486 treatment, while there was a reduction in the Dolichos biflorus agglutinin lectin binding, indicating inhibition of the normal secretory transformation of the endometrium. It is likely that these effects on endometrial development and secretory activity represent the basis of the contraceptive effect of post-ovulatory RU486 treatment.

PIP: The aim was to evaluate further the effect of a single, immediate, post-ovulatory dose of RU-486 on endometrial maturation at the time of implantation. A total of 11 healthy women, 21-40 years old, with regular menstrual cycles, volunteered for the study (height 167 cm; weight 66 kg). None of them had used steroidal contraceptives or an IUD for a minimum of 3 months prior to the study. The study included 1 control cycle and 1 or 2 treatment cycles, the subjects serving as their own controls. During the 1st treatment cycle, 200 mg mifepristone (RU-486) were given orally between 8 and 10 p.m. on cycle day LH+2. Four subjects participated in a 2nd treatment cycle in which the dose of RU-486 was increased to 400 mg. Blood samples were obtained 3 times weekly during the entire study period and were analyzed for estradiol and progesterone by radioimmunoassay. One endometrial tissue specimen was obtained in the control and the treatment cycle(s) from the anterior and lateral walls of the uterine cavity using a Randall curette. The secretory components of endometrial glands were detected by lectin cytochemistry using biotinylated Dolichos biflorus agglutinin (DBA) and the Vectastain Elite ABC immunoperoxidase detection system. The treatment did not disturb the menstrual cycle, but it produced profound endometrial changes in all subjects. A histological pattern corresponding to the proliferative phase was seen in 7 subjects, whereas 2 others demonstrated irregular secretory activity, and 2 biopsies showed a pattern corresponding to LH+4. Significantly decreased glandular diameter (p 0.01), as well as increased number of glandular (p 0.01) and stromal (p 0.01) mitoses, occurred in comparison with biopsies taken in the control cycle. In all endometrial specimens examined after RU-486 treatment there was a reduction in the DBA staining. The profound effects of RU-486 on endometrial development and secretory activity are most likely the underlying reason for the contraceptive effect of RU-486 when administered immediately following ovulation.

A new reliable method of culturing and measuring human decidual capillary endothelial cells.

A reliable method of culturing human decidual capillary endothelial cells was developed. Endothelial growth cell supplement, heparin and newborn bovine serum were added to the culture medium to facilitate growth. Decidual capillary endothelial cell cultures showed similar growth curves to the more traditional human umbilical cord vein endothelial cell cultures. Culture growth was assessed by a new morphometric method of measuring cell culture area with the use of a computerised measuring tablet. This new method was compared with the more laborious method of counting individual cells and was found to be as reliable and more efficient.

Studies on a vaginal ring releasing levonorgestrel at an initial rate of 27 micrograms/24 h when used alone or in combination with transdermal systems releasing estradiol.

Vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24h were studied in a group of 24 normally menstruating women during three months (i.e., during three four-week segments). Each segment consisted of three weeks with the vaginal rings in situ followed by a treatment-free period of one week. The women were divided into three groups (8 subjects each). The first group received vaginal rings only, the second and third groups were treated, in addition, with transdermal systems (patches) releasing estradiol at a rate of 50 and 100 micrograms/24h, respectively. Peripheral blood samples were withdrawn three times weekly (Monday, Wednesday and Friday) during a pretreatment cycle and during the following three months of treatment. The levels of L-NOG, estradiol and progesterone were analyzed by radioimmunoassay techniques. In all subjects, endometrial biopsies were taken in a control cycle and during the last days with vaginal rings in situ in segments II and III. The treatment with estradiol did not significantly influence L-NOG levels. Considerable differences in the L-NOG levels between the subjects of the same group were observed. Fluctuation in ovarian reaction within groups was also large. Nevertheless, estradiol noticeably increased the proportion of anovulatory cycles; the total number of anovulatory segments was 5, 9 and 19 (out of 24) in the groups "No estradiol", "50 micrograms/24h estradiol" and "100 micrograms/24h estradiol", respectively. A morphometric study of the endometrium indicated a significant decrease in the diameter of glands. This change was due to L-NOG alone, but it seemed to be accentuated by the exogenous estradiol. The occurrence of glandular mitoses increased in both groups receiving estradiol in a dose-dependent manner, indicating an increased endometrial proliferation. The treatment with estradiol did not significantly alter the bleeding pattern.

Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study.

The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a group of 12 normally menstruating women during 90 days of continuous use (i.e., during three 30-day treatment segments). Blood samples were drawn immediately before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after insertion of the rings, and thereafter three times weekly throughout the study for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment. The peak of average L-NOG levels was reached within two hours after the insertion of rings. Until 24 h after insertion, the levels did not change significantly. Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was a significant (p < 0.001) decrease of SHBG levels due to treatment. During the total of 36 treatment segments, a normal ovarian function was seen in 47% of the segments. The women were anovulatory and had an inadequate lutal function in 28% and 25% of segments, respectively. No correlation between the L-NOG levels and ovarian reaction to treatment was found. The use of L-NOG induced significant changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02) and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence of vacuolated cells decreased significantly (p < 0.02 and p < 0.005, respectively). None of the endometrial parameters or dating was correlated with the ovarian reaction to treatment, indicating independent endometrial effects of L-NOG.

Morphological characteristics of preimplantation stage endometrium in the rhesus monkey.

The morphological characteristics of endometrium on day 6 after ovulation of conception (group 1) and non-fecund, menstrual (group 2) cycles have been studied in the rhesus monkey (n = 30). A conception cycle was distinguished by the presence of a developmentally normal, age-stage-synchronized embryo. Thus, 78% of the mated cycles (n = 18) yielding synchronous embryos (12 zona-encased and two zona-free blastocysts) were used for this study. On day 6 after ovulation, no significant changes in the serum concentrations of oestrogen and progesterone were seen in conception cycles (n = 14) compared with the non-mated, normal ovulatory cycles (n = 12). Morphometric analyses revealed that on day 6 of gestation (n = 8), endometrium differed from the corresponding non-mated luteal phase (n = 7) with significant increases in epithelial mitosis (P < 0.01), height of glandular epithelium (P < 0.05), volume ratio of gland cell to gland (P < 0.03), degree of pseudostratification (P < 0.02), and higher frequency of supranuclear, adluminal accumulation of vacuoles in gland cells (P < 0.05). The degree of stromal oedema was higher (P < 0.02) in fecund cycles but there was no change in venular diameter. In a separate set of experiments, estimates of tissue vascular response revealed a higher (P < 0.02) endometrial extravascular albumin space on the same day of gestation; there were no differences, however, in endometrial blood volume, or in the number of von Willebrand antigen-positive capillaries and small vessels between the two groups (group 1, n = 6; group 2, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

A poisoned inheritance to our children.

PIP: The editorial by Henry J. Leese published in the October 1992 issue of Human Reproduction dealt with the problems of world population growth. The United Nations Population Fund publication on the state of world population 1990 declared that, at the start of the 1990s, decisive action is needed to top population growth, attack poverty, and protect the environment. The world's population was 5.3 billion in 1993. According to projections, southern Asia will account for 31% of the total increase of the world's population and Africa for 23% during the next 10 years. Developed countries like Europe, the former Soviet Union, North America, and Japan will account for only 6% of the increase. In 1969-1971, the total number of malnourished was 460 million, and it is projected to increase to 532 million by the end of this century. The total number of illiterates is projected to rise from 742 million in 1985 to 889 million by year 2000. During the last decade, the income per person has risen significantly in east Asia, where population has grown most slowly. In Africa, where the population has increased very fast, the income per capita has grown least. The World Fertility Survey in 1990 showed that less than 25% of women in 23 out of 38 countries had larger families than they would have desired. A survey in 1987 revealed that, in developing countries, 45.3% of contraception was sterilization, 23.1% was the IUD, and only 15.5% used hormonal contraception. In developed countries, sterilization accounted for 14.2% of contraception, IUDs for only 7.8%, and hormonal contraceptives for 18.4%. In East Asia, 93% of people have an acceptable access to a variety of contraceptive methods, 57% in South East Asia and Latin America, whereas in sub-Saharan Africa, only 9%. Worldwide, less than 30% of the contraceptive users rely on methods for male contraception, e.g., withdrawal, condoms, vasectomy or abstinence. The WHO Special Program of Research on Human Reproduction and the Population Council are researching for a male contraceptive vaccine.^ieng

Morphometric characteristics of endometrial biopsies after different types of ovarian stimulation for infertility treatment.

OBJECTIVE: To investigate whether various types of ovarian stimulation induce differences in endometrial development at the midluteal phase in infertile women. DESIGN: Assessment of stromal and glandular compartments in endometrial biopsies using morphometric criteria. SETTING: Institute for Hormone and Fertility Research, Hamburg, Germany. PATIENTS: The study included 18 women after treatment with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) (group I), 23 women after clomiphene citrate (CC)/hMG/hCG treatment (group II), and 12 women after CC stimulation (group III). INTERVENTIONS: Endometrial biopsies and blood samples were taken simultaneously in the early to midluteal phase. To assess the time of ovulation, hormone analysis and regular checks by ultrasonography were performed. MAIN OUTCOME MEASURES: Morphometric evaluation of glandular and stromal structures revealed an impaired endometrial development after various treatment protocols. CONCLUSION: Ovarian stimulation in infertile women results in most cases in an elevation of steroid levels; however, the occurrence of an inadequate endometrial development might have an unfavorable influence on the outcome of implantation. Therefore, these findings may be of importance to the choice of treatment for infertility.