Improvement of spontaneous pregnancy rate after stopping gonadotropin therapy for anovulatory infertility

In a prospective study, 140 patients with infertility because of ovulatory factors (group A) were followed up for 6 months after failure to achieve pregnancy using human menopausal gonadotropin (hMG) therapy. They included cases of oligomenorrhea, polycystic ovarian disease (PCOD), and hypogonadotropic amenorrhea. They were treated with hMG alone or in combination with clomiphene citrate or gonadotropin-releasing hormone agonist analog. The control group (B) included 83 infertile patients because of similar ovulatory factors. They were followed up for 6 months not preceded by ovulation induction. The overall pregnancy rate (PR) in group A (20.7%) was significantly higher than group B (7.2%). The PR was significantly higher in oligomenorrhea and PCOD patients when compared with the control group. There was no significant difference in the hypogonadotropic group.     

Combined pregnancy after gonadotropin therapy

Three cases of combined pregnancy are described after gonadotropin therapy; two cases after human pituitary gonadotropin and one after human menopausal gonadotropin administration. In each case the intrauterine gestation was a multiple pregnancy. After salpingectomy, two of the women have proceeded to the delivery of healthy infants; the third woman aborted. In each case the gonadotropin stimulation regimen was ceased at the appropriate stage when the estriol excretion was between 60 and 125 micrograms/day, but the subsequent rate of rise of estriol was 2.3- to 3.2-fold during the coasting phase before the human chorionic gonadotropin trigger when the estriol excretion rate was 140 to 350 micrograms/day.     

Improvement of cervical factor by high-dose estrogen and human menopausal gonadotropin therapy with ultrasound monitoring

Conventional treatment of the cervical factor has proved unsuccessful, with fertility rates under 30% usually quoted. Low-dose estrogen has been one of the main therapies but carries the complication of ovulation interference. It is hypothesized that higher doses of estrogen would improve mucus but would have an even greater adverse effect on ovulation. However, the latter could be obviated by concomitant use of human menopausal gonadotropin (hMG). The hMG would then be monitored by pelvic ultrasound because the ingested estrogen would interfere with estrogen assays. Eighty-two percent of 34 infertile women with no motile sperm on baseline postcoital tests improved their levels after therapy with this high-dose estrogen hMG technique. To date, 56% of these women for whom therapy had previously failed have conceived. Nevertheless, simpler and less expensive techniques should be used initially.     

Antihypertensive therapy in pregnancy directed by noninvasive hemodynamic monitoring

Invasive and noninvasive investigations suggest that the hemodynamics of pregnant hypertensive patients are heterogeneous. Nineteen pregnant patients were evaluated before changes in antihypertensive therapy. Cardiac output was measured by Doppler technique. Blood pressure was measured by automated cuff. Systemic vascular resistance was calculated. Two distinct groups were identified on the basis of differences in cardiac output (p less than 0.0001) and systemic vascular resistance (p less than 0.0001). Those with high resistances were treated with hydralazine. A modest antihypertensive effect was achieved (-6.9 mmHg, p = 0.01), but systemic vascular resistance was dramatically reduced, (-534 dyne.sec.cm-5, p less than 0.0001) and was associated with a compensatory increase in cardiac output (2.0 liters/min, p less than 0.0001). Those with a high cardiac output were treated with atenolol. An antihypertensive effect was achieved, (-17.0 mm Hg, p = 0.008), which was associated with a reduction in cardiac output (-2.8 liters/min, p less than 0.0001).     

Hydatidiform mole in a triplet pregnancy following gonadotropin therapy

A first case is reported of complete hydatidiform mole with two coexistent fetuses in a triple pregnancy following human menopausal gonadotropin human chorionic gonadotropin (hMG-hCG) therapy. The molar mass and two fetuses were delivered separately at 17 weeks of gestation. The fetuses were female (155 g) and male (160 g) with individual placentae (85 g, 90 g). The hydatidiform mole (650 g) had a normal 46,XX karyotype. The sexes of the two fetuses and the karyotype of the mole are consistent with previous reports that the chromosomes of fetuses and moles are derived from both parents and the father, respectively.     

Conception rate after gonadotropin therapy in hyperprolactinemia and normoprolactinemia

The cumulative pregnancy rate after gonadotropin treatment was evaluated in 63 hyperprolactinemic and 242 normoprolactinemic women. All pregnancies in the hyperprolactinemic patients were achieved within four treatment cycles; the cumulative pregnancy was 62% as compared with 29% in normoprolactinemics. The same results were obtained when patients were divided according to endogenous estrogenic activity. These results imply that in bromocriptine failures there is no need to lower prolactin levels to achieve pregnancy with gonadotropins.     

Are estrogen assays essential for monitoring gonadotropin stimulant therapy?

Ovarian responses to human menopausal gonadotropin (hMG) are conventionally monitored by urinary estrogen or serum estradiol (E2) concentration. E2 can also be measured in saliva but this is rarely used. With ultrasound (USS) however, follicular development is assessed directly and we have previously shown that USS is superior to urinary estrogens for monitoring. We have now compared salivary and serum E2 with USS during hMG therapy in 48 women over 101 cycles. Salivary and serum E2 correlated significantly with each other and with the number of mature follicles. The manufacturers of hMG state that hCG should be given only when E2 is between 100 and 3000 pmol/l. However, there were no mature follicles in 40% of the cycles where E2 lay within this range. USS is the most accurate method of monitoring responses to hMG and, where this is available, estrogen assay provides no additional useful information.     

Regulation of gonadotropin secretion by monitoring energy availability

Nutrition is a principal environmental factor influencing fertility in animals. Energy deficit causes amenorrhea, delayed puberty, and suppression of copulatory behaviors by inhibiting gonadal activity. When gonadal activity is impaired by malnutrition, the signals originating from an undernourished state are ultimately conveyed to the gonadotropin‐releasing hormone (GnRH) pulse generator, leading to suppressed secretion of GnRH and luteinizing hormone (LH). The mechanism responsible for energetic control of gonadotropin release is believed to involve metabolic signals, sensing mechanisms, and neuroendocrine pathways. The availabilities of blood‐borne energy substrates such as glucose, fatty acids, and ketone bodies, which fluctuate in parallel with changes in nutritional status, act as metabolic signals that regulate the GnRH pulse generator activity and GnRH/LH release. As components of the specific sensing system, the ependymocytes lining the cerebroventricular wall in the lower brainstem integrate the information derived from metabolic signals to control gonadotropin release. One of the pathways responsible for the energetic control of gonadal activity consists of noradrenergic neurons from the solitary tract nucleus in the lower brainstem, projecting to the paraventricular nucleus of the hypothalamus. Further studies are needed to elucidate the mechanisms underlying energetic control of reproductive function.     

Ovulation and successful pregnancy in a woman with ovarian failure after hypophysectomy and gonadotropin therapy

A 38-year-old woman ovulated and conceived after administration of human menopausal gonadotropins despite a previous diagnosis of ovarian failure at age 18. Possible explanations include restoration of down-regulated gonadotropin receptors by development of a prolactinoma, spontaneous remission of autoimmune oophoritis, or prior tumor secretion of biologically inert gonadotropins.     

The value of ultrasound for monitoring ovarian responses to gonadotropin stimulant therapy

Ultrasonic measurement of ovarian follicles was used in conjunction with conventional measurement of urinary oestrogen output to monitor responses in infertile women receiving gonadotrophin stimulant therapy. In the 21 women who conceived during the first 15 months, in which this combined monitoring was used, ultrasound proved superior to oestrogen measurement alone for assessing follicular maturity and hence deciding when to administer the ovulating dose fo chorionic gonadotrophin. The use of ultrasound imaging improves efficiency of treatment with gonadotrophin stimulant therapy, but is not predictive of multiple pregnancy or of hyperstimulation.     

Human chorionic gonadotropin and free beta subunit secretion in three events of pregnancy.

Serum hCG and free beta hCG subunit were measured in intrauterine pregnancies (n = 21), ectopic pregnancies (n = 20) and spontaneous abortions (n = 19) matched for gestational age. Significantly higher concentrations of both dimer and free beta subunit hCG were detected in normal pregnancies (86,336 IU/L) and 21.02 IU/L respectively) compared to abortions (10,460 IU/L and 3.73 IU/L) and ectopic pregnancies (3,900 IU/L and 3.73 IU/L) (p less than .05). When the ratio of free beta hCG/intact hCG (%) was studied, however, EP had significantly higher ratios (0.09 +/- 0.09) than IUP (p less than .05). Assessment of the relative distributions of these ratios revealed that 100% of IUP and AB and 65% of EP had ratios less than 0.10. Most notably, 35% of EP were uniquely characterized by ratios greater than 0.10. This ratio was sufficiently higher in 35% of EP to define a profile completely unique to EP. These data suggest that an increased free beta to dimer hCG ratio of greater than 0.10 may assist in the differentiation of ectopic from intrauterine pregnancies of spontaneous abortions and provide insight into a possible trophoblastic mechanics in these clinical events.     

The efficacy of early pregnancy monitoring with serial chorionic gonadotropin determinations and real-time sonography in an infertility population

Ninety-one pregnancies were monitored prospectively with serial human chorionic gonadotropin (hCG) determinations and real-time sonography. The monitoring process included an initial hCG doubling time (DT) followed by sonographic examination for fetal heart motion at 7 to 8 weeks in the asymptomatic patient. In women with an abnormal DT or who developed symptoms, repeat hCG determinations and/or sonography were performed. A single DT correctly identified 95% of the successful pregnancies (58) and 64% of the abnormal pregnancies (25 abortions and 8 ectopic gestations) in asymptomatic women. With repeat hCG determinations and/or sonography, 88% of the spontaneous abortions (before aborting) and 100% of the ectopic pregnancies (before tubal rupture) were identified. As a result of the early diagnosis, conservative surgery was performed in six of eight women with tubal pregnancies. The presence of fetal heart motion was a reliable indicator that an intrauterine pregnancy will progress to viability in both the symptomatic (89%) and asymptomatic patient (93%). We conclude that the combined use of serial hCG determinations and real-time sonography provides efficacious monitoring of the early high-risk pregnancy.     

Ovulation induction by human menopausal gonadotropin with ultrasonic monitoring of the ovarian follicles

One hundred sixteen cycles of human menopausal gonadotropin (hMG) treatment for ovulation induction were studied. The ovarian response to hMG treatment was monitored by the daily determination of serum estradiol (E2) or by daily serum E2 and repeated ultrasonic examination of the ovaries. There were more follicles 18 mm in diameter or larger at the time of human chorionic gonadotropin (hCG) administration in the pregnancy than in the non-pregnancy cycles, and in the hyperstimulated than in the nonhyperstimulated cycles. The ovulatory rate and the pregnancy rate per cycle did not improve with the use of ultrasound. The number of treatment cycles required to achieve pregnancy was less in patients who had ultrasonic examination of the ovarian follicles. These results suggest that ultrasonic examination of the ovarian follicle helps to reduce the number of hMG cycles required to achieve pregnancy. The development of multiple follicles results in more pregnancies. However, the use of ultrasound does not improve the pregnancy rate.