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Biomedical subjects

J Blankstein

Publications and source records attributed to J Blankstein.

At least 37 records · Page 2Linked to original sources

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↗

The role of early post-implantation beta-HCG levels in the outcome of pregnancies following in-vitro fertilization.

Daily plasma beta-HCG levels from days 11 to 18 after ovum retrieval (OR) were evaluated in a group of 73 women who became pregnant following in-vitro fertilization and embryo replacement (IVF-ER). The 47 patients who had a normal ongoing pregnancy could be distinguished from the 26 patients with a pathological pregnancy (pre-clinical abortion, clinical abortion and tubal pregnancy) by the mean daily beta-HCG levels, their mean daily increase and the intercept and slope of the beta-HCG regression analysis. The mean daily beta-HCG levels of the normal pregnancies were significantly higher than: (i) pre-clinical abortions on days 12-18 after OR; (ii) clinical abortions on days 12-16; and (iii) tubal pregnancies on days 12-17. Using quadratic discriminant analysis, normal and pathological pregnancies could also be distinguished by their absolute beta-HCG levels on day 13 after OR with 27.6 mIU/ml being the cut-off point. Our results indicate that the outcome of pregnancy following IVF-ER could be predicted with a high degree of probability by monitoring daily beta-HCG levels within the first 2 weeks following OR.

Adult↗

Protocols for induction of ovulation. The concept of programmed cycles.

Programmed oocyte retrieval which includes suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives or GnRH analogue and predetermined ("fixed") day for ovum pick-up has been demonstrated to yield a pregnancy rate that is comparable to that achieved by the conventional individualized approach to follicular maturation. We have prospectively compared two regimens of suppression (the pill and GnRH analogue) followed by two ovarian stimulation protocols (clomiphene citrate + human menopausal gonadotropin [CC + hMG] and pure follicle-stimulating hormone + human menopausal gonadotropin [pure FSH + hMG]). Sixteen patients were studied in each group. It was found that the latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression, and that suppression with the GnRH analogue was associated with a shorter latent phase than that with the pill. Suppression with the pill for 30 days compared with 15 days resulted in a greater cancellation of laparoscopic oocyte retrieval, a lower fertilization rate, and a lower pregnancy rate. The numbers of oocytes recovered, fertilized, and cleaved were similar in both stimulation protocols. The use of the GnRH analogue for 30 days compared with 15 days was associated with a lower pregnancy rate, even though the number of oocytes that were recovered and fertilized were similar. Ovarian stimulation with pure FSH + hMG resulted in a shorter latent phase than did stimulation with CC + hMG, but the results of treatment with both protocols were similar. It is concluded that both the pill and GnRH analogue are acceptable means of manipulating the cycle and the day of oocyte retrieval. However, they should be used for the shortest periods possible because prolonged use is associated with some unwarranted effects. For each suppression-stimulation protocol there seems to be a different fixed day for retrieval that should be established prospectively.

Chorionic Gonadotropin↗

The effect of clomiphene citrate and tamoxifen on the cervical mucus.

The anti-estrogenic effect of clomiphene citrate (CC) and tamoxifen (TMX) on cervical mucus was evaluated in a prospective crossover study. Ten women underwent randomized alternate cyclical treatment with either 100 mg CC, 40 mg TMX daily, or with placebo. The effect of CC, TMX and placebo on serum estradiol (E2), cervical mucus secretion and on the development of ovarian follicles was evaluated. Compared with placebo, treatment with CC and TMX significantly increased the number of mature ovarian follicles on the day of assumed ovulation (p less than 0.05), elevated E2 secretion (p less than 0.05) and decreased cervical score (p less than 0.05). It can be concluded that anti-estrogenic agents reduced the secretion of cervical mucus. However, in most cases, the excessive E2 production due to multiple follicular growth overcomes the anti-estrogenic effect.

Adult↗

Induction of ovulation in the patient with polycystic ovarian disease.

Induction of ovulation is difficult to achieve in patients with PCOD when they are resistant to therapy with clomiphene citrate; moreover, treatment with human menopausal gonadotropins subjects the PCOD patient to the risk of multifollicular ovulation and hyperstimulation. This article summarizes the hormonal picture and the initial therapeutic approach to the patient with PCOD. The proper administration, usage, and monitoring of conventional ovulation-inducing agents for these patients are discussed. Some of the newer approved agents that can be used in special patients who have not responded to conventional ovulation induction are also described.

Androgens↗

The influence of different copper wires on human sperm penetration into bovine cervical mucus, in vitro.

The influence of four different copper-containing intrauterine devices (IUD) (Nova-T, Multiload, Fincoid 250 and copper-T 250) on the penetration of human sperm into bovine cervical mucus were assessed. Pooled samples of predetermined sperm concentration were suspended in Earl's medium in which a copper IUD was previously incubated for periods between one hour to fourteen days. The mean copper concentration was determined for each of the medium containing IUD and was found to be between 284 +/- 93 micrograms/100 ml to 392 +/- 138 micrograms/100ml. While there was no adverse effect on sperm motility by the copper-containing medium, there was a significant reduction in the number of sperm penetrated into the bovine cervical mucus as compared to the penetration of sperm suspended in pure Earl's medium. It therefore seems that the influence of copper on sperm penetration might be by an effect on the environment or spermatozoal migration rather than by direct effect of copper on sperm motility.

Adult↗

Ovarian hyperstimulation syndrome: prediction by number and size of preovulatory ovarian follicles.

Monitoring of human menopausal gonadotropin (hMG) treatment for induction of ovulation according to either preovulatory estrogen levels or the presence of a dominant ovarian follicle was found insufficient to prevent ovarian hyperstimulation syndrome (OHS). In 65 infertile patients treated with hMG and human chorionic gonadotropin (hCG), a possible correlation between the number and size of all ovarian follicles on the day of assumed ovulation and the occurrence of OHS was evaluated in order to assess the value of ultrasonography in predicting OHS. It was found that patients with OHS had significantly more follicles at the time of hCG than patients without OHS. Mild OHS was characterized by the presence of eight to nine follicles, 68.7% of which were of intermediate size (9 to 15 mm). In moderate to severe OHS 95% of the preovulatory follicles were less than 16 mm, most of them (54.7%) less than 9 mm in diameter. It can be concluded that a specific preovulatory follicular configuration characterizes mild and severe hyperstimulation. This is important information before hCG administration and emphasizes the value of ovarian ultrasonography in predicting OHS.

Chorionic Gonadotropin↗

Rescue of menotrophin cycles prone to develop ovarian hyperstimulation.

In an attempt to prevent the loss of 'overstimulated cycles' associated with human menopausal gonadotrophin (hMG)-induced ovulation, oestradiol levels and ovarian follicular state were monitored in 12 women with 'overstimulated cycles' after withholding hMG for several days. Human chorionic gonadotrophin (hCG) was administered when oestradiol levels were less than or equal to 1700 pg/ml and the leading follicles between 17 and 22 mm in diameter. During the withholding period follicular growth continued in all patients, while oestradiol levels declined in all but three. These three patients conceived. Ovulation was observed in six additional women. Ovarian hyperstimulation did not occur in any of the 12 patients. We conclude that a rescue of 'overstimulated cycles' is sometimes possible. Conception seems to depend on a continuing rise of E2 levels and early detection of 'overstimulation'.

Chorionic Gonadotropin↗

Changing pituitary reactivity to follicle-stimulating hormone and luteinizing hormone-releasing hormone after induced ovulatory cycles and after anovulation in patients with polycystic ovarian disease.

Pituitary reactivity to GnRH, characteristic of polycystic ovarian disease (PCOD), has been attributed both to a primary ovarian cause and to hypothalamic-pituitary dysfunction. If the heightened pituitary reactivity characteristic of PCOD patients is secondary to chronic anovulation, ovulatory cycles should produce changes in the LH to FSH ratio and reduce the augmented response to GnRH. In a randomized cross-over study of 10 women with PCOD, GnRH (100 micrograms) was injected iv on the fifth day of 2 consecutive cycles, 1 of them following anovulation and progesterone withdrawal bleeding and the other following an induced ovulatory cycle. Mean basal plasma 17 beta-estradiol, progesterone, and FSH levels were similar after ovulatory and anovulatory cycles. However, mean basal serum testosterone (P less than 0.05) and LH (P less than 0.01) levels were significantly lower, as were LH levels 30, 60, and 90 min (P less than 0.01) and FSH levels 60 and 90 min (P less than 0.05) after GnRH injection, after an ovulatory cycle than after an anovulatory cycle. The pituitary response to GnRH in those PCOD patients, therefore, was more normal after an ovulatory cycle than after an anovulatory cycle. We conclude that the heightened pituitary reactivity characteristic of PCOD patients is associated with chronic anovulation.

Adult↗

Abolishment of the positive feedback mechanism: a criterion for temporary medical hypophysectomy by LH-RH agonist.

The hypothalamic pituitary axis was studied in patients with an abnormal pattern of gonadotropin release during chronic treatment with LH-RH agonist. Two patients had PCOD and the third demonstrated the early luteinization phenomenon. Following a well-defined gonadotropin rise with initiation of LH-RH treatment, no further response was noted. Stabilization of the LH:FSH ratio in PCOD patients was noted after 4 weeks of treatment. Administration of both native LH-RH (100 micrograms) and intravenous pulsatile LH-RH did not evoke any rise in LH. In addition to the above LH-RH challenges, the positive feedback was examined by administration of estradiol benzoate (EB). The study demonstrated that, although the pituitary did not respond to any LH-RH challenge, it may still respond by a rise in LH following EB administration. Both functions of the hypothalamic pituitary axis should be examined in order to determine the state of medical hypophysectomy.

Administration, Intranasal↗