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Biomedical subjects

J Blankstein

Publications and source records attributed to J Blankstein.

At least 19 recordsLinked to original sources

Psychological follow-up of women evaluated as oocyte donors.

Forty-five women were evaluated as candidates to donate oocytes to an infertile couple. Twenty-four women completed a cycle as oocyte donors. Follow-up data on donor satisfaction were obtained for 23 women. Ninety-one per cent were moderately to extremely satisfied with the experience and 74% would donate for another cycle if given the chance. Transient adverse psychological symptoms were reported by two donors but were resolved with medical or psychological treatment. Two women became pregnant soon after donation, one unintentionally. Psychological risk factors predicted donor candidates' decisions to participate and their compliance but were not predictive (within the group that completed a cycle) of donor satisfaction as follow-up or recipient pregnancy.

Adult

Hormonal profiles and follicular growth in cycles with imminent ovarian hyperstimulation.

Ovarian hyperstimulation syndrome is a common and serious complication of human menopausal gonadotrophin/human chorionic gonadotrophin treatment. We evaluated the changes in the pituitary and ovarian hormone profiles and ultrasonographic follicular regression in 12 patients in whom human menopausal gonadotrophin was discontinued due to 'imminent' ovarian hyperstimulation. Following discontinuation, three distinct periods were observed: (i) days 1-2, the levels of oestradiol, testosterone and prolactin, and the total number of follicles continued to rise; (ii) days 3-6, the levels of oestradiol, testosterone and prolactin declined sharply and the total number of follicles was reduced significantly, while the large and medium sized follicles continued to increase. Levels of follicle-stimulating hormone and luteinizing hormone gradually declined to reach their lowest levels by days 5-6 and then increased. (iii) Thereafter the number of follicles and steroid output declined to early follicular phase levels. We conclude that discontinuation of human menopausal gonadotrophin and withholding human chorionic gonadotrophin in cycles with laboratory signs of 'imminent' ovarian hyperstimulation syndrome, allows regression of the ovarian ultrasonographic finding and prevents the development of clinical symptoms. However, if rescue of the cycle is attempted, human chorionic gonadotrophin should be given during the first 4 days after discontinuation of stimulation.

Adult

Failure to improve ovarian response by combined gonadotropin-releasing hormone agonist and gonadotropin therapy.

Nineteen women were treated with the gonadotropin-releasing hormone (GnRH) agonist buserelin in order to suppress the pituitary prior to gonadotropin treatment. Eight women were oligomenorrheic, 6 had polycystic ovarian disease (PCOD) and 5 women had normal cycles. Buserelin was administered for 3 weeks before ovarian stimulation, and the pituitary down-regulation was proven by provocative tests. Ovarian stimulation was then achieved by human menopausal gonadotropin (hMG) 2 ampules a day. Several abnormal responses to the combined buserelin/hMG treatment were noted in some patients. This included a sudden decrease in E2 level without LH surge (2 patients), induced follicular growth with buserelin instead of ovarian suppression (2 patients) and ovarian hyperstimulation syndrome in 3 patients with PCOD. From this we conclude that although pituitary suppression can easily be achieved by GnRH analog administration, this does not ensure the prevention of unwanted responses. It is possible that the common denominator for these abnormal responses is that they are ovarian in origin, hence they occur in spite of pituitary down-regulation. Close monitoring of the suppression and stimulation stages will detect most cases of such failures. Furthermore it is possible that not all patients are suitable for the combined treatment of gonadotropin and GnRH agonist.

Adult

Steroid secretion by granulosa cells isolated from a woman with 17 alpha-hydroxylase deficiency.

Steroid synthesis in luteal/granulosa cells harvested after follicular aspiration in a patient with 17 alpha-hydroxylase deficiency was investigated. Follicular stimulation with purified FSH after the suppression of ACTH and gonadotropin secretion by corticoid analogs and superactive GnRH agonist permitted ovum pick-up and the study of steroid synthesis in the obtained granulosa cells. Progesterone synthesis was elevated while 17 alpha-hydroxy progesterone, testosterone, androstenedione, and estrogen production was minimal. Aromatase activity was retained in these cells, as demonstrated by the 100-fold increase in estrogen levels after the addition of androgens. Progesterone levels in follicular fluids were in the normal range, while estrogen, 17 alpha-hydroxy progesterone, and androgen levels were minimal. These results provide in vitro evidence of 17 alpha-hydroxylase deficiency in the granulosa cells of this patient.

Adrenal Hyperplasia, Congenital

Addition of exogenous estrogens to improve cervical mucus following clomiphene citrate medication. Patient selection.

Medication with Clomiphene Citrate and its effects on the quality of cervical mucus and the addition of exogenous estrogens in order to suppress abnormal mucus secretion are controversial issues. We have prospectively studied a group of 19 anovulatory women who were treated with clomiphene citrate in order to characterize those patients most likely to respond to the addition of exogenous estrogens. On day 14 of the cycle, 17 beta estradiol and cervical score were measured and 1 mg estradiol benzoate was injected intramuscularly. Cervical scores were below 7 in 12 out of the 19 patients before estradiol benzoate administration. In these patients, 17 beta estradiol rose from 751 +/- 541 to 1321 +/- 648 pg/ml (p less than 0.03), and cervical scores rose from 3.75 +/- 2.1 to 7.1 +/- 3.7 (p less than 0.01), after estradiol benzoate administration. Patients with cervical scores of 8-12 did not improve significantly. In the 12 patients with cervical scores below 7, those (n = 6) with 17 beta estradiol below 600 pg/ml experienced a significant improvement in cervical score, in contrast to those (n = 6) with 17 beta estradiol above 600 pg/ml who had no improvement. The reduction in cervical mucus accomplished with clomiphene citrate can be further improved by adding exogenous estrogens, mainly in patients who have low 17 beta estradiol levels concomitant with low cervical score.

Anovulation

The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies.

We carried out a prospective, randomized, double-blind, placebo-controlled study to investigate the capacity of aspirin to prevent pregnancy-induced hypertension and to alter prostaglandin metabolism. A total of 791 pregnant women with various risk factors for pre-eclamptic toxemia were screened with use of the rollover test (a comparison of blood pressure before and after the woman rolls from her left side to her back) during week 28 or 29 of gestation. Of 69 women with abnormal results (an increase in blood pressure during the rollover test), 65 entered the study and were treated with a daily dose of either aspirin (100 mg; 34 women) or placebo (31 women) during the third trimester of pregnancy. The number of women in whom pregnancy-induced hypertension developed was significantly lower among the aspirin-treated than among the placebo-treated women (4 [11.8 percent] vs. 11 [35.5 percent]; P = 0.024); the same was true for the incidence of preeclamptic toxemia (1 [2.9 percent] vs 7 [22.6 percent]; P = 0.019). The mean ratio of serum levels of thromboxane A2 to serum levels of prostacyclin metabolites after three weeks of treatment decreased by 34.7 percent in the aspirin-treated group but increased by 51.2 percent in the placebo-treated group. No serious maternal or neonatal side effects of treatment occurred in either group. We conclude that low daily doses of aspirin taken during the third trimester of pregnancy significantly reduce the incidence of pregnancy-induced hypertension and pre-eclamptic toxemia in women at high risk for these disorders, possibly through the correction of an imbalance between levels of thromboxane and prostacyclin.

Adult

Increased human menopausal gonadotropin dose during the early follicular phase: effect on follicular recruitment and treatment outcome.

To investigate whether the provision of increased gonadotropins would enhance follicular recruitment and selection, women not responding (N = 18) to our standard clomiphene citrate (CC)-human menopausal gonadotropin (hMG) regimen were treated with increased hMG (treatment cycle II). Estradiol levels were higher in treatment cycle II and these differences were significant on days 8 and 9 (P less than or equal to 0.05 and P less than or equal to 0.03, respectively). On day 9, better follicular development was seen in cycle II (P less than or equal to 0.05). While none of the patients responded in cycle I, 10 of 18 responded in cycle II. Of the 10 responders, 2 conceived following in vitro fertilization and embryo placement. Increasing the dose of hMG improved the development of a cohort of follicles so that aspiration and possible pregnancy were achieved in women who were previously unresponsive to therapy.

Clomiphene

Combined clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in a fixed schedule for follicular recruitment during in vitro fertilization: effects on premature luteinizing hormone (LH) surges.

Recognizing the association between plasma progesterone (P) and an imminent LH surge, we investigated the frequency of P elevation in our stimulation protocol (clomiphene citrate-human menopausal gonadotropins). P was measured retrospectively on the day before, the day of, and the day after human chorionic gonadotropin hCG administration. The means +/- 2 standard deviations for P were as follows: day before hCG, 0.58 +/- 0.86; day of hCG, 0.64 +/- 0.56; and day after hCG, 1.47 +/- 1.22. Seven patients (8%) had P levels greater than 2 SD above the mean. Significant P elevations prior to hCG are infrequent with this protocol, and in the few patients with raised P a trend toward lowered fertilization was noted. The low incidence of P elevation may be secondary to the administration of hCG in a timely manner on the sixth day of estradiol (E2) rise.

Chorionic Gonadotropin

Hot flushes during Gn-RH analogue administration despite normal serum oestradiol levels.

Five out of 6 normally-menstruating women who were treated with a potent gonadotropin-releasing hormone (Gn-RH) agonist in order to achieve medical hypophysectomy developed hot flushes despite having normal oestradiol (E2) levels. The Gn-RH agonist was administered subcutaneously for 6 days and then intranasally for a further 14 days. A dose of 2 mg of E2 benzoate was injected intramuscularly once a week for 2 consecutive weeks. This combined treatment resulted in low peripheral gonadotropin levels but normal serum E2 concentrations. Four (4) women developed mild to moderate hot flushes and there was 1 case of flushes severe enough to necessitate cessation of treatment. The flushes occurred in the second week of Gn-RH analogue treatment when the level of serum luteinizing hormone (LH) was low and the pituitary was unresponsive to provocative tests, despite the fact that the patients' E2 levels were normal (mean 250 +/- 25 pg/ml). It is suggested that neither LH pulsatility nor low peripheral E2 levels are mainly responsible for the development of hot flushes. It is possible that Gn-RH, a hypothalamic decapeptide, may play a major role or act as a mediator in the aetiology of hot flushes.

Administration, Intranasal

Pituitary and ovarian suppression rate after high dosage of gonadotropin-releasing hormone agonist.

Ten infertile menstruating women were treated with daily injections of gonadotropin-releasing hormone agonist (GnRH-a). The GnRH-a (Buserelin; Hoe 766, Hoechst-AG, Frankfurt/Main, West Germany) was administered subcutaneously (SC) from day 9 of the cycle for 6 days, and intranasally (1.2 mg) for 15 days. Before treatment, all ten women had a normal response to Buserelin challenge test and the GnRH test, and seven of the ten responded to estradiol (E2) benzoate test (2 mg intramuscularly). The SC administration of Buserelin (1.5 mg) for 6 days resulted in suppression of pituitary activity. Continuous treatment with Buserelin (1.2 mg for 3 weeks) was effective as demonstrated by decreasing serum E2 levels to below 20 pg/ml, and in the absence of ovarian follicles in ultrasonographic scanning. Three days after cessation of Buserelin treatment, the pituitary again responded to the GnRH test. Thus, the authors concluded that the administration of Buserelin in very high doses can induce medical hypophysectomy within 6 days, but over 3 weeks of suppression therapy are required to abolish ovarian findings. Desensitization of the pituitary was reversible within 3 days of cessation of the treatment.

Adult

A program for matched, anonymous oocyte donation.

The authors' program for matched, anonymous oocyte donation has resulted in two successful pregnancies among the first eight oocyte recipients. All oocyte recipients to date have had ovarian failure or absence with premature ovarian failure the most common cause. All recipients were cycled on a program of incremental oral micronized estradiol and intramuscular progesterone-in-oil. Thirteen candidates for oocyte donation were screened to obtain 8 donors. One donor candidate was excluded because of her medical history. The psychological screening of 2 of the other donor candidates (who subsequently did not complete the donation cycle) revealed a primary motive of financial gain. In general, the psychological profiles of donor candidates revealed a high incidence of troubled families and either reproductive loss or loss of a parent. Ovarian stimulation of the donors followed our standard in vitro fertilization protocol. The recipients' exogenous steroid replacement continued until days 97 and 101, respectively, of the two gestations. Both pregnancies resulted in the delivery of normal singleton males--the first at 40 weeks, the second at 35 weeks.

Adult

The role of gonadotropins in the etiology of ectopic pregnancy.

Our study indicates that the high rate of EP in MAP(+) patients, treated with hMG/hCG, is due to the fact that it is a selected group of infertile patients with probable additional underlying tubal disease. Absence of EP in MAP(-) patients indirectly support the theory that a mechanical factor is at work. It is, therefore, our opinion, that the cause of ectopic pregnancy lies in the patient and not in the drug (hMG/hCG).

Chorionic Gonadotropin

Comparison of five clomiphene citrate dosage regimens: follicular recruitment and distribution in the human ovary.

One hundred fifty-six women with cycle disorders presenting as absence or infrequency of ovulation and with luteal phase deficiency (group II, according to the World Health Organization classification) received clomiphene citrate (CC) for ovulation induction. The administered dosage ranged from 50 to 250 mg/d. The follicular development in terms of numbers of small (less than 8 mm), intermediate (9 to 15 mm), and large (greater than 15 mm) follicles and their distribution in either one or both ovaries on the day of assumed ovulation was related to the dosage of CC. A statistically significant increase was found in the total number of follicles in relation to the dosage of CC (P less than 0.003). In view of the development of the mature follicles, the gradual increase in CC daily dosage was thought to be associated with additional mature follicles before ovulation. However, this increased follicular recruitment was not regarded as statistically significant. Treatment with low doses of CC resulted in follicular development in only one ovary, whereas increased follicular recruitment after high CC dosage was found in association with follicular development in both ovaries.

Clomiphene

In vitro fertilization and primary embryonic cleavage are possible in 17 alpha-hydroxylase deficiency despite extremely low intrafollicular 17 beta-estradiol.

Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in genotypic females is characterized by primary amenorrhea and the absence of sexual maturation due to inadequate biosynthesis of ovarian androgens and estrogens. We induced ovarian follicular development in a woman with this syndrome. Ovum pick-up, in vitro fertilization, and primary embryonic development were achieved despite undetectable plasma estradiol and extremely low ovarian androgen concentrations and minute concentrations of these hormones in the ovarian follicular fluid.

Adrenal Hyperplasia, Congenital

Programmed oocyte retrieval: clinical and biological effects of oral contraceptives administered before in vitro fertilization.

We have prospectively compared two regimens of suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives (OCs) for 15 or 30 days and two ovarian stimulation protocols. The latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression. Thirty days' suppression, compared with 15 days', resulted in the cancellation of more cycles and a lower fertilization and pregnancy percentage. No significant increase in either serum progesterone or luteinizing hormone was noted in suppressed cycles. It is concluded that if programming is desired, OCs should be used for the shortest period possible. The variation in the length of the follicular phase indicates that there is a different 'fixed' day for retrieval for each suppression-stimulation protocol and this day should be established prospectively.

Adult

Pure follicle stimulating hormone does not enhance follicular recruitment in clomiphene citrate/gonadotropin combinations.

Patients beginning an in vitro fertilization (IVF) treatment cycle were prospectively randomized in double-blind fashion to receive either follicle-stimulating hormone (FSH) (Metrodin, Serono Laboratories, Inc., Randolph, MA) (n = 50) or human menopausal gonadotropin (hMG) (Pergonal, Serono) (n = 48) in combination with clomephene citrate (CC) (Serophene, Serono). There were no statistically significant differences in the percentage of dropped cycles, follicular response as measured by serum estradiol or ultrasound imaging, cycle day for hCG administration, number of oocytes recovered, fertilization and cleavage rates of the recovered oocytes, or the rate of clinical pregnancy establishment. In conclusion, there were no clinically important differences between FSH and hMG when combined with CC for enhanced follicular recruitment for IVF. Therefore, there is no apparent justification for the use of FSH in CC combination regimens, considering FSH's increased cost as compared with hMG.

Adult

The anovulatory patient. An orderly approach to evaluation and treatment.

Ovulatory dysfunction is a leading cause of female infertility in the United States. Fortunately, ovulatory dysfunction is often amenable to treatment. Thorough testing is necessary to identify the exact cause of anovulation before conventional ovulation-inducing therapy is started. Careful patient monitoring is essential to avoid risks such as the ovarian hyperstimulation syndrome. Several newer ovulation-inducing agents are available for use in special situations.

Anovulation