Abortion rate in pregnancies following ovulation induced by human menopausal gonadotropin/human chorionic gonadotropin

Despite the high incidence of fetal loss following gonadotropin therapy, the etiologic, factors that contribute to this loss remain unknown. In 203 women who conceived following gonadotropin therapy, the abortion rate was 28.5%. However, in 84 women who conceived a second time, also with gonadotropin treatment, the abortion rate was 11.9%. Second- and third-degree hyperstimulation of the ovary are accompanied by a 50% abortion rate, and the occurrence of abortion is more frequent in the first pregnancy. The contribution of multiple pregnancy, maternal age, and number of gonadotropin treatment cycles are also evaluated and discussed.     

Spontaneous pregnancy and its outcome after human menopausal gonadotropin/human chorionic gonadotropin-induced pregnancy

The fertility in previously sterile women who conceived at least once following hMG/hCG-induced ovulation is investigated. The study comprises 141 women. The cumulative spontaneous pregnancy rate (CSPR) was calculated using life table analysis and was found to be 30.4% after 5 years. The CSPR for subsequent pregnancies reached 91.3% after 5 years. This figure is similar to that of normal parous women, although the study group (previously infertile women) requires a larger exposure period to attain the figure. The spontaneous abortion rate in the hMG/hCG-induced pregnancies was 29%; whereas in subsequent spontaneous pregnancies this rate was 8.8%. This difference in rate was found to be statistically significant, and the possible reasons are discussed.     

Successful quadruplet pregnancy following ovulation induced with human menopausal gonadotropin and human chorionic gonadotropin

A case report of a quadruplet pregnancy that followed the induction of ovulation by human chorionic gonadotropin and human menopausal gonadotropin is presented. Examination revealed 4 separate placentas, indicating development from 4 different ova. The infants all did well at term, with no signs of respiratory distress syndrome, and have developed normally. Early diagnosis by ultrasonography and complete early bedrest are important for fetal survival. Hospitalization at Week 27-28 of pregnancy is essential, and a complete, competent staff able to handle high-risk patients should be available. Intravenous ethanol infusion is useful during early labor. The patient must be carefully observed for postpartum hemorrhage and should be followed in the recovery room for 24 hours.     

Luteinizing hormone bioactivity in human menopausal gonadotropin/human chorionic gonadotropin-induced cycles

Eight human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG)-induced cycles in four anovulatory women unresponsive to clomiphene citrate plus hCG were studied. Blood samples were obtained for baseline determinations and daily thereafter, 24 hours after the injection of hMG. Serum estradiol (E2), progesterone, follicle-stimulating hormone, and luteinizing hormone (LH) were measured by radioimmunoassay. Bioassayable LH (LH-b) was determined by the immature mice interstitial cell in vitro bioassay for testosterone with LER-907 as the reference standard. Appropriate follicular growth, assessed by pelvic ultrasonography, occurred in all cycles. During induction days mean immunoassayable LH (LH-i) and LH-b levels were suppressed until the E2 concentrations rose to a mean of 1420.5 +/- 149 pg/ml (standard error of the mean), at which time a concurrent rise in LH-b and LH-i levels was observed (130% and 34%, respectively). LH-b/LH-i ratio increased by 63% on the day E2 peaked, indicating enhanced LH bioactivity before hCG administration. Our data suggest that during hMG/hCG-induced cycles, in a high E2 milieu, endogenous or exogenous LH may show a heterogeneity in its molecular content, resulting in enhanced bioactivity relative to immunoactivity.     

Advanced endometrial maturation after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin for in vitro fertilization

Endometrial biopsy was performed between the first and third luteal phase day in 22 normally cycling patients following human menopausal gonadotropin and human chorionic gonadotropin ovulation induction for in vitro fertilization but in whom embryo transfer was not accomplished. Eleven patients showed an "advanced" pattern and 10 an "in-phase" endometrium according to the Noyes criteria. A significant difference in serum progesterone levels on days 16 and 18 was found in these two groups. Serum progesterone levels were significantly higher by day 18 if pregnancy was established. In in vitro fertilization and embryo transfer the embryo arrives 24 to 48 hours earlier than in natural conception in the endometrial cavity. Therefore, the "advanced" endometrium may have some benefit for embryo implantation.     

Vital initiation of pregnancy (VIP) using human menopausal gonadotropin and human chorionic gonadotropin ovulation induction: phase II--1981

In a program for in vitro fertilization, laparoscopies for oocyte aspiration were performed on 24 patients receiving human menopausal gonadotropin and human chorionic gonadotropin. Of the 40 preovulatory oocytes that were recovered from these patients, 33 (83%) were fertilized and 30 (75%) cleaved and were transferred. Ten immature oocytes were collected, and attempts were made to mature these in vitro prior to insemination. All ten oocytes (100%) did fertilize, and seven (70%) cleaved and were transferred. Morphologic variation was noted between cleaving conceptuses, even in those conceptuses responsible for establishing pregnancies. Five pregnancies resulted from 19 embryo transfers (26%).     

Vital initiation of pregnancy (VIP) using human menopausal gonadotropin and human chorionic gonadotropin ovulation induction: Phase I--1981

Laparoscopies for oocyte aspiration in 31 cycles were performed on 25 patients receiving human menopausal gonadotropin and human chorionic gonadotropin. Sixty oocytes were aspirated, of which 48 were considered preovulatory. Ninety-seven percent (58 of 60) of the oocytes were found in the original aspirate, and the remaining oocytes were found in either the first or second follicle wash. The fertilization rate per preovulatory oocyte was 33% (16 of 48), whereas on a per cycle basis it was 39% (12 of 31). A total of 15 conceptuses (2-cell = 5; 3-cell = 3; 4-cell = 7) were transferred to 12 patients, and two pregnancies were established. These pregnancies were established by transfers of 3-cell and 4-cell conceptuses at approximately 47 hours after insemination. Both pregnancies resulted in term deliveries of normal infants.     

Influence of weight in the induction of ovulation with human menopausal gonadotropin and human chorionic gonadotropin

Patients failing to ovulate and conceive on clomiphene citrate (CC) or CC plus human chorionic gonadotropin (hCG) or patients with pituitary gonadotropin deficiency are candidates for human menopausal gonadotropin (hMG) plus hCG therapy. The duration and number of ampules needed to stimulate ovarian response leading to ovulation and/or pregnancy vary individually. Seventy-one patients who had complete follow-up evaluation and accurately documented body weights at the time of therapy were considered for the study. Of these 71 patients, 41 (57.3%) conceived in 293 cycles. The average number of ampules of hMG used by patients with 10% to 20% below ideal body weight (IBW) was 13.9 +/- 6.3 (mean +/- standard deviation [SD]). The average number of ampules used by patients with normal +/- 10% IBW was 14.2 +/- 3.5. Patients who were overweight by 10% to 25% used 15.3 +/- 5.4 ampules, and patients overweight by greater than or equal to 25% used 20.9 +/- 5.6 ampules of hMG. Eleven patients with severe hypothalamic chronic anovulation needed an average of 20.6 +/- 6.2 ampules. The data reveal a direct relationship between IBW and the amount of hMG needed to induce ovulation and/or pregnancy; however, in the presence of chronic hypoestrogenic conditions, it is expected that these patients will need higher amounts of hMG, regardless of body weight.     

Ovarian hyperstimulation syndrome following ovulation induction with human menopausal gonadotropin

Twenty-seven anovulatory women who had episode(s) of ovarian hyperstimulation during ovulation induction with hMG were studied. Twenty-nine of the total 89 treatment cycles were complicated by ovarian hyperstimulation. Twenty-four-hour urinary estrogen concentrations 3 days prior to hCG administration were significantly higher in the hyperstimulated (H) than in the nonhyperstimulated cycles (NH). Patients who had progesterone withdrawal bleeding (Group I) were more prone to be hyperstimulated in the first treatment cycle than patients who had no progesterone withdrawal bleeding (Group II). In all instances, the syndrome resolved spontaneously with time. The pregnancy rate of H was threefold NH. It is concluded that hyperstimulation in patients who had evidence of endogenous estrogen activity as demonstrated by progesterone withdrawal bleeding tend to occur in the first treatment cycle. Strict monitoring decreased the incidence of severe hyperstimulation. A minimal amount of hyperstimulation might be beneficial to improve the pregnancy rate.     

Delaying human chorionic gonadotropin administration in human menopausal gonadotropin-induced cycles decreases successful in vitro fertilization of human oocytes

Correct timing of human chorionic gonadotropin (hCG) administration in induced cycles for in vitro fertilization is of crucial importance to oocyte maturation and normal luteal function. The purpose of this work was to compare the effect of hCG timing on follicular development, oocyte maturation, and fertilization in vitro, as well as on the pattern of luteal phase hormone secretion. Ovulation was induced in 32 normally cycling women by human menopausal gonadotropin (hMG)/hCG administration. In the first group (17 women) 10,000 IU hCG was administered 24 hours after the last injection of hMG and in the second group (15 women) 48 to 72 hours after the last hMG injection. Serum estradiol levels prior to oocyte aspiration were similar in both groups, as were the numbers of large follicles on the day of hCG administration (4.5 +/- 2.3 versus 4.1 +/- 1.9 follicles/woman, respectively). The distribution of oocyte-corona-cumulus complexes was similar in both groups and was comprised of 11% immature, 43% intermediate, and 45% mature complexes. The fertilization rate, however, was significantly (P less than 0.001) reduced in the group treated by delayed hCG injection (57% versus 84%), and the percentage of degenerated oocytes was increased (9% versus 1%). Luteal phase length as well as progesterone and estradiol levels were comparable in both groups. It is concluded that an interval longer than 24 hours between the last injection of hMG and the administration of an ovulatory dose of hCG does not affect follicular and luteal phase serum steroid patterns but may result in a decreased oocyte fertilization rate, possibly due to atretic changes in the follicles.     

Endometrial inadequacy after treatment with human menopausal gonadotropin/human chorionic gonadotropin

The incidence of abnormal endometrial histology in patients undergoing human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) treatment during cycles of in vitro fertilization (IVF) or gamete intrafallopian transfer has been reported to be 52% to 91%. The incidence of endometrial inadequacy, as judged by a single late luteal endometrial biopsy, has not been studied in hMG/hCG non-IVF cycles. In the current study, 30 patients (30 cycles) undergoing hMG/hCG treatment were evaluated by an endometrial biopsy. The incidence of endometrial inadequacy was found to be 27%. No preovulatory predictors for endometrial inadequacy could be identified. Therefore, luteal support for patients undergoing non-IVF hMG/hCG cycles should be considered.     

Disappearance of human chorionic gonadotropin and resumption of ovulation following abortion.

The disappearance of human chorionic gonadotropin (hCG) and resumption of pituitary ovarian function was investigated in 13 patients following first- and second-trimester abortions. First-trimester abortion patients (with suction curettage) had a mean time of 37.5 +/- 6.4 days for the clearance of hCG to a level of 2 mlU/ml. Second trimester abortions (with prostaglandin) had a mean time of 27.4 +/- 4.8 days. Patients undergoing second-trimester hysterectomy had a mean disappearance time of 39.7 +/- 5.3 days and only 12 days if the hysterectomy was initiated with ligation of the uterine and ovarian vessels. No significant difference in clearance time was found when it was compared on the basis of the baseline hCG levels. Based on a concomitant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peak, nine of 12 patients resumed normal pituitary function. These LH and FSH peaks were seen even though the serum hCG levels were as high as 35 mlU/ml. Based on serum progesterone levels of greater than 3 ng/ml, all these nine patients ovulated as early as 21 days after abortion. In view of these results, the clearance of hCG after pregnancy termination depends mainly upon the type of procedure used. Moreover, in view of the early time of ovulatory recovery, contraception should be instituted within the first 2 weeks following pregnancy termination.     

Disappearance of human chorionic gonadotropin following removal of ectopic pregnancy

A study was undertaken to determine the length of time serum beta-subunit of human chorionic gonadotropin (beta-hCG) could be detected following removal of ectopic pregnancy. Seven patients underwent complete removal of trophoblastic tissue by either salpingectomy or partial resection of the involved fallopian tube. Nine other patients had conservative surgical treatment by either linear salpingostomy or fimbrial expression of the fallopian tube. Serum beta-hCG levels were determined serially in all these patients. The results demonstrate that the initial titer of hCG is a significant factor in determining the length of time that it can be detected in the serum postoperatively. In addition, decreasing titers, conforming to the disappearance curve of hCG, as constructed in this study, are a helpful aid in avoiding further surgery in the group of patients who had a conservative removal of the trophoblastic tissue. Finally, the serum clearance of hCG by radioimmunoassay may take at least up to 24 days after surgery.     

Management of multiple conceptions after gonadotropin-releasing hormone analog/human menopausal gonadotropin/human chorionic gonadotropin therapy

The treatment course of a 31-year-old infertility patient due to PCO disease is presented. Because the patient failed to conceive after various treatment cycles with CC, she was subjected to a combined GnRHa/hMG/hCG therapy. After plasma E2 levels had reached 2400 pg/ml, three leading follicles, with diameters of 20 to 24 mm, were detected. Induction of ovulation was achieved by 10,000 IU hCG. The patient conceived and developed ovarian hyperstimulation. At 8 weeks of gestation, seven cystic structures were detected within the uterine cavity, five containing single embryos, and two with twin embryos. All nine embryos were vital, as evidenced by their heart beats. Embryo reduction was achieved by transabdominal puncture on three occasions. The three surviving fetuses were carried to the 34th week of gestation. After delivery by cesarean section, three healthy babies developed normally. This communication illustrates the complications that can be associated with ovulation induction in PCO disease: ovarian hyperstimulation, polyovulation, multiple conceptions, and their clinical management.     

Transient hyperprolactinaemia in human menopausal gonadotropin induction of ovulation

In 20 anovulatory patients who were normoprolactinaemic, 12 developed transient hyperprolactinaemia when they were treated with human menopausal gonadotropin (hMG) for induction of ovulation. The hyperprolactinaemia was probably due to the increased oestrogen production effect on some susceptible patients. The pregnancy rate was found to be lower in those who developed this condition. The dosage of hMG required was found to be significantly higher in this group. The importance of recognizing this transient hyperprolactinaemia and the probably role of Bromocriptine are discussed. Further study is suggested.