Fetal outcome of triplets in a Turner mosaic.

Pregnancies are now being reported resulting from fertilization of donor oocytes in women with ovarian failure. A case of triplets in a Turner mosaic is reported herein following transfers of embryos resulting from donor oocytes. She had previously demonstrated a normal sized uterine cavity by hysterosalpingography. The opinion from our group was that she should consider selective reduction but a perinatology consult thought she should have a favorable outcome. Her pregnancy was complicated by polyhydramnios, pre-term labor, and eventual fetal demise at 25 and 27 weeks of all three fetuses. Natural pregnancies in patients with gonadal dysgenesis have been reported in at least 138 patients. Many aborted or had stillbirths and this high rate of fetal mortality has been ascribed to chromosomal abnormalities. The continued use of donor oocytes will provide data to evaluate whether there will continue to be a higher spontaneous abortion rate and complications in second and third trimesters in Turner's pregnancies even in single pregnancies. The outcome of this case can at least be provided to future gonadal dysgenesis patients with triplets to help them in their decision as to whether or not to have selective reduction.

A conservative treatment protocol with human menopausal gonadotropins aimed at reducing multiple births.

In multicenter studies involving 3002 courses of human menopausal gonadotropins (hMG) therapy in 1286 patients, 20% of the patients who delivered had multiple gestations; 75% of these were twins and 25% were triplets or higher parity. Our stimulation regimen is very conservative in that we 1) try to allow a female with LPD and regular cycles but not reaching a mature follicle to first select her dominant follicle and wait until the serum E2 reaches approximately 100 pg/mL then add the hMG. With anovulatory women we frequently begin with only 75 IU hMG and gradually increase the hMG dosage. Using this approach we have usually attained at least a 70% pregnancy rate in six months. A study was performed to see if this conservative approach resulted in a decreased multiple birth rate percentage especially with triplets or more. The study was to evaluate the outcome of 241 consecutive pregnancies in which hMG was the sole therapy. There were 203 with one gestation and 38 with multiples. Twins--32; triplets--6. Thus 15% (38/241) had multiple births; six of 38 (15%) of the multiples had triplets or more. Though our multiple birth rate and especially higher parity rate appears to be lower than average no statistical difference was found. Thus even with conservative use of hMG multiple births cannot be easily avoided.

Evidence that difference in size of fraternal twins may originate during early gestation: a case report.

We describe a woman who conceived by in vitro fertilization (IVF) and embryo transfer (ET). Transvaginal ultrasound demonstrated at least 1 week's difference in size of twin gestations from 1 month post-transfer of embryos to delivery. Differences in sac size, crown-rump length, and gestational growth are discussed, as are implications of ultrasound in early pregnancy.

Comparison of short versus long-term leuprolide acetate--human menopausal gonadotrophin hyperstimulation in in-vitro fertilization patients.

The use of leuprolide acetate for at least 10 days beginning in the mid-luteal phase prior to initiating human menopausal gonadotrophin (HMG) stimulation has been fairly successful in preventing cancellations for premature luteinization and allowing retrieval of more oocytes, which in turn provide more embryos for cryopreservation. However, it is theoretically possible that the long-term use of leuprolide may have some adverse effect on either pregnancy rates or on mean survival after cryopreservation and thawing. Recently, a short 3 day regimen of a gonadotrophin-releasing hormone agonist, buserelin effectively prevented premature luteinization during HMG stimulation. The present study indicated that substitution of a 3 day course of leuprolide acetate also effectively prevented premature luteinization but was less expensive, required statistically fewer ampoules of HMG and much less leuprolide.

Premature luteinization: treatment and incidence in natural cycles.

The incidence of premature luteinization was evaluated in 400 women with a history of infertility (greater than or equal to 18 months). After its diagnosis, this condition was treated with ovulation-inducing drugs in the early follicular phase in an attempt to accelerate follicular maturation before the luteinizing hormone (LH) surge. Premature luteinization was diagnosed if serum progesterone levels greater than 1.5 ng/ml were associated with an LH surge before the serum oestradiol level reached 200 pg/ml and before the follicle was mature. Fifty-two of 400 (13%) women demonstrated premature luteinization in two consecutive cycles. Fourteen of 52 (27%) women corrected the problem with a clomiphene citrate regimen, as compared with 32 of 38 (75%) treated with HMG and HCG; conception rates were 83 and 50%, respectively, for the patients who responded to the two regimens. Overall, regimens utilized in this study resulted in a 58% pregnancy rate in 6 months.

Serum progestagen-associated endometrial protein (PEP) levels in conception versus nonconception cycles following in vitro fertilization-embryo transfer.

The human endometrium synthesizes a specific protein known as the progestagen-dependent endometrium protein (PEP) which rises from early to late luteal phase. The PEP levels follow the pattern of the endometrial biopsy more than the serum progesterone (P) levels (4). Late luteal-phase serum PEP levels were evaluated as well as serum P in mid-luteal phase in patients undergoing IVF-ET. Comparisons were made between conceivers and nonconceivers and between aborters and nonaborters. Both serum PEP and late luteal P levels were significantly higher in pregnant patients but no differences in mid luteal P levels were seen. No difference was seen in aborters vs nonaborters. It is still inconclusive whether the higher late luteal PEP levels contribute to the greater likelihood of pregnancy or are a result of the pregnancy.

Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea.

The efficacy of a technique of gonadotropin suppression and human menopausal gonadotropins (hMG) to induce ovulation in women with hypergonadotropic amenorrhea was evaluated in 100 consecutive women. Ovulation was achieved in 19% of cycles (68/361), the pregnancy rate per cycle was 5.2% (19/361), and the viable pregnancy rate was 2.2% (8/361). In the majority of the successful cases, estrogen was used to decrease the elevated luteinizing hormone and follicle-stimulating hormone levels, especially where the ethinyl estradiol therapy alone induced a rise in endogenous 17 beta-estradiol levels with hMG used to boost the follicle to maturation. Although the success rate is low, this technique can result in some successes in otherwise almost hopeless cases.

Amenorrhea in an ovulatory woman despite a normal uterine cavity: case report.

A 35-year-old nulliparous woman came to us for treatment of amenorrhea. Evaluation demonstrated normal ovulation with appropriate results of sequential endometrial biopsies during the luteal phase. The only abnormality found was an elevated serum level of follicle-stimulating hormone in the early follicular phase, and it is hypothesized that this somehow leads to atrophy of the endometrium without shedding.

Empirical therapy of the male with clomiphene in couples with unexplained infertility.

Unexplained infertility may be secondary to a cryptic male or female factor. Although most often empirical therapy of the female partner may be attempted, clomiphene has been claimed, after uncontrolled studies, to improve fertility in men with subnormal spermograms. We chose to determine if clomiphene therapy of the male would improve fertility in couples with unexplained infertility despite normal-appearing semen parameters. One hundred husbands were randomized to treatment with clomiphene citrate, 25 mg daily for 25 days with 5 days' rest each month, if their social security numbers ended in an even number or ascorbic acid, 500 mg daily, if ending in an odd number. All female infertility factors had to be meticulously corrected for at least eight cycles for inclusion in the study, along with a minimum of 1 1/2 years' duration of infertility. Within 8 months, 29 of 50 couples (58%) with clomiphene therapy of the male achieved a pregnancy, but only 8 of 50 (16%) with ascorbic acid treatment of the male. There were no appreciable changes in sperm counts, motility, or morphology after either treatment, nor were there any significant differences in semen parameters in those conceiving versus those who did not. Further, improved fertility could not be accounted for by improvement in the hamster ova penetration test. Possibly, clomiphene improves some quality of the sperm that is defective but not measurable by standard androgenologic methods, or it improves some aspect of the seminal plasma. Perhaps, though, the results might be better explained on a psychogenic basis, i.e., clomiphene is a "better" placebo than ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical evaluation of the Pipelle endometrial suction curette for timed endometrial biopsies.

A clinical study was performed to determine the efficacy of the Pipelle in obtaining endometrial samples to be analyzed for luteal function. Patients' tolerance of this instrument and their willingness to undergo subsequent biopsies were also ascertained. An endometrial sample was obtainable from 1,278 women with the Pipelle, whereas 52 required the Novak curette and in 60 the sample could not be obtained with either instrument. Thirteen percent of the patients biopsied with the Pipelle stated that they would not allow a second such procedure to be performed. One percent of the samples were deemed inadequate for hormonal reading. The Pipelle seemed to be a safe, minimally traumatic method of sampling the endometrium for hormonal evaluation.

Ovulation induction and pregnancy with an estrogen-gonadotropin stimulation technique in a menopausal woman with marked hypoplastic ovaries.

A case is described of a woman with ovarian failure and documented atrophic ovaries in whom ovulation was achieved with the use of high-dose estrogen and human menopausal gonadotropins. The proposed mechanism involves a reduction in the elevated gonadotropins, which restored an adequate number of receptors. Thus sensitivity to exogenous menotropins was reestablished.

Pregnancy in premature ovarian failure after therapy with oral contraceptives despite resistance to previous human menopausal gonadotropin therapy.

We report the case of a 35-year-old woman with premature ovarian failure that was documented at 29 years of age, who wanted to conceive. Although she failed to respond to high doses of menotropin therapy, she ovulated and conceived after she took an oral contraceptive. The oral contraceptive was used to reduce the elevated level of gonadotropins in an effort to restore receptors to the luteinizing hormone and follicle-stimulating hormone, which theoretically may have been down-regulated.

False-positive human chorionic gonadotropin levels caused by a heterophile antibody with the immunoradiometric assay.

A case of a false-positive test for the beta-subunit of human chorionic gonadotropin as performed by the immunoradiometric assay is described. Further studies revealed that this problem was secondary to a cross-reacting heterophile antibody.

The importance of laparoscopic coagulation of mild endometriosis in infertile women.

To evaluate the effect of fulguration of endometriotic implants in patients with mild endometriosis, we divided 123 patients into two groups: (A) patients whose endometriotic implants were coagulated, and (B) patients whose implants were left intact. In group A, 42 of 69 (60.8%) patients achieved a pregnancy within eight cycles following laparoscopic fulguration, in comparison with 10 of 54 (18.5%) patients from group B. The difference between this study and others is that all other infertility factors were meticulously corrected prior to laparoscopic treatment, and patients were allowed at least eight "normal" cycles before their endometriosis was treated. This is a report of 8 months' postoperative follow-up. The study was prospective and treatment was assigned randomly. We feel that laparoscopic fulguration significantly improves fertility in these carefully selected patients.

First-trimester serum levels of the beta-subunit of human chorionic gonadotropin in a tubal molar pregnancy.

A woman is described in whom the levels of the beta-subunit of human chorionic gonadotropin were rising in a pattern consistent with a tubal pregnancy. A tubal molar pregnancy was found. Thus an early ectopic molar pregnancy is not distinguishable from a nontrophoblastic tubal pregnancy on the basis of human chorionic gonadotropin levels.

Spontaneous abortion rate in patients with endometriosis treated with progesterone.

Several reports suggest that women with endometriosis have a higher risk of spontaneous abortions when left untreated; however, these studies did not control for the presence of possible luteal phase defects. This study was designed to document the frequency of spontaneous abortions in women with endometriosis and ovulation defects treated prophylactically with progesterone, compared with similar patients without endometriosis. All the women had late luteal phase endometrial biopsies dating perfectly normal. Our findings show an increase in the rate of spontaneous abortions (25.7%) in women with endometriosis as compared with the entire group (3.8%). However, when the result for the group with endometriosis is compared with the subgroup of patients at diagnostic laparoscopy not showing endometriosis, the results are similar (30%). We conclude that when properly matched groups are compared, there is no increased risk of spontaneous abortions in women with endometriosis. Since we perform laparoscopies only in women failing to conceive after a reasonable number of seemingly normal cycles, the apparently high incidence of abortions in this group may be secondary to other factors that not only may lengthen the time needed for conception but also increase the abortion risk after conception.

Progesterone therapy to decrease first-trimester spontaneous abortions in previous aborters.

A study was designed to see if the use of prophylactic progesterone vaginal suppositories (PVS) reduced the risk of spontaneous abortions in women with a history of at least one spontaneous abortion. PVS was employed during the luteal phase to the end of the first trimester. The dosage was initially 50 mg/day, but was increased according to the endometrial biopsy and doubled as soon as pregnancy was established. Only 10 women (10%) aborted, and 8 of these 10 were successful in their next PVS-treated pregnancies. Overall there were 12 losses in 132 pregnancies (9%) in these PVS-treated patients. Forty-two percent of untreated controls aborted (10/24). The results suggest that PVS is effective in reducing the risk of spontaneous abortions in high-risk patients.

The efficacy of progesterone in achieving successful pregnancy: I. Prophylactic use during luteal phase in anovulatory women.

We have previously shown that prophylactic supplementation of progesterone beginning in the luteal phase of patients treated with human menopausal gonadotropins (hMG) could reduce the risk of spontaneous abortions. The present study was initiated with 100 patients to evaluate the efficacy of a new progesterone therapeutic regime in patients requiring either hMG or clomiphene citrate. A significantly decreased risk of spontaneous abortion (6% vs. 28%) was seen in 50 patients prophylactically treated with progesterone as compared with 50 control patients. The progesterone regimen was then tried on 566 consecutive patients who were treated and conceived with hMG or clomiphene citrate, and approximately the same risk (6.2% by 20 weeks) was found. This incidence of spontaneous abortion is even less than the accepted risk for the general population.

Diagnosis and treatment of the cervical factor. I. Improvement with a short-course treatment of high-dose estrogen.

A new technique for improving cervical factor is described. This technique employs the use of high-dose estrogen at the time that a mature follicle is determined by ultrasound in patients who have inadequate postcoital tests despite the use of low-dose estrogen, guaifenesin, and tetracycline. Previously, a technique based on high-dose estrogen early in the follicular phase was employed; this suppressed pituitary gonadotropins, thus requiring the concomitant use of hMG. Seventy-three percent of the patients for whom this more expensive and intricate technique would have been necessary were able to achieve a good postcoital test through this modified technique of merely using high-dose estrogen when the follicle has already matured. Thirty-three percent achieved a pregnancy within 6 months on this therapy.

Diagnosis and treatment of the cervical factor. II. Employment of pelvic sonography in diagnosis.

A study was performed to evaluate the relationship between the postcoital test, follicle size, and the basal body temperature (BBT). We found 17% of the patients to have good postcoital tests before the rise in the BBT, at which time, however, the follicle was still too small. By the time the follicle reached maturity, the mucus quality regressed to poor. The problem was corrected in 88% of the patients by the human menopausal gonadotropin (hMG)-high-dose estrogen technique, and 53% achieved pregnancies. Twenty-two percent had a poor postcoital test just before the rise in the BBT. However, ultrasound data indicated that ovulation had already taken place, and the mucus had been of good quality a few days before, when the follicle was at the proper size. Thus, ultrasound may be useful in eliminating false positive and negative cervical factor diagnoses, and is also helpful in some new techniques for treating the cervical factor.