Search PubMed⌕ Search

Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 73 records · Page 4Linked to original sources

Diagnosis, prevention and management of ovarian hyperstimulation syndrome.

The overall incidence of clinically important (moderate to severe) OHSS ranges from 1% to 10% of IVF cycles, but only a small proportion (0.5% to 2%) of the cases are severe. In extreme but rare cases, secondary complications such as deep vein thrombosis, respiratory distress and acute hepato-renal failure may occur. The main risk factors are the presence of polycystic ovaries, high ovarian response to superovulation therapy, the use of hCG to trigger the ovulatory process or for luteal phase support, and the endogenous production of hCG by an early pregnancy. The pathogenesis of OHSS is unknown, although the predominant biochemical mediator is thought to be the renin-angiotensin system. Ovarian stimulation should always be carefully monitored to identify those women at risk. In IVF cycles, the hCG injection should be withheld if the risk is judged to be too great. Some women will benefit from a policy of proceeding to collect oocytes, but electively cryopreserving any resulting embryos, thus allowing the ovarian stimulation cycle not to be wasted. The administration of albumin at the time of oocyte collection will reduce the chance of severe OHSS occurring. If a decision is made to proceed with oocyte recovery and embryo transfer, it may be advisable to give 5000 IU of hCG, rather than 10,000 IU, as the ovulatory trigger. Progesterone, and not hCG, should be given in the luteal phase. Women developing mild or moderate OHSS should be kept under outpatient surveillance to detect the minority that may progress to severe OHSS. Those with severe OHSS should be hospitalised for fluid and electrolyte management. Paracentesis under ultrasound guidance is recommended where there are tense ascites, but further surgical intervention should rarely be undertaken and only when there is good clinical evidence of ovarian torsion or haemorrhage.

Female↗

Balancing the risk of recurrent thromboembolism and pre-existing osteoporosis in pregnancy.

In summary, our 31-year-old patient with hypogonadotrophic hypogonadism has severe osteoporosis caused by chronic oestrogen deficiency. Her GnRH deficiency can be overcome using ovulation induction therapy. However, if she becomes pregnant there is a small risk of recurrent thromboembolism because of her previous cerebral thrombosis. This risk is hard to quantify but would undoubtedly increase if her mobility were impaired. The metabolic and mechanical alterations of pregnancy may compromise her weakened skeleton and increase the risk of a second major fracture. Her skeletal status precludes the use of standard heparin. Fractionated low molecular weight heparins would be the prophylactic agent of choice, possibly switching to low-dose warfarin for the second trimester. Alternative prophylaxis using low-dose aspirin may be suitable, although this is not proven. The difficulty in this case is that pregnancy and the prophylactic measures designed to protect the patient may prove to be detrimental. The case also highlights the vital role of prepregnancy counselling and interdisciplinary consultation between obstetrician, haematologist and endocrinologist in order to steer the safest course through this therapeutic minefield.

Adolescent↗

Cumulative conception and live-birth rates after in vitro fertilization with and without the use of long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin.

OBJECTIVE: Our purpose was to compare cumulative conception and live-birth rates after in vitro fertilization with and without the use of the long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin. STUDY DESIGN: Life-table analysis of conception and live-birth rates in relation to ovarian stimulation regimen used in 2893 women who had one of five stimulation regimens exclusively throughout all treatment cycles, namely, human menopausal gonadotropin with or without clomiphene citrate; follicle-stimulating hormone with or without clomiphene citrate; and long, short, and ultrashort protocols of buserelin, plus follicle-stimulating hormone or human menopausal gonadotropin; and in an additional 347 women who had been administered both human menopausal gonadotropin and follicle-stimulating hormone with or without clomiphene citrate. RESULTS: The cumulative conception rate and cumulative live-birth rate were significantly higher in those women treated exclusively with the long buserelin regimen (59% and 55%, respectively, after three cycles) compared with those who only had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (39% and 29%, respectively, after three cycles) (p = 0.001 and p = 0.0001) or compared with those who had only short or ultrashort buserelin regimens (22% and 17% after two cycles) (p = 0.0001 and p = 0.005). The pregnancy failure rate in patients on the long buserelin regimen was 22.4% (95% confidence interval 14.8% to 30.0%) compared with 33.3% (95% confidence interval 29.6% to 37.0%) in those who had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (p = 0.03). When the probabilities of first conception and first live birth were examined by treatment regimen, after we allowed for the effects of age, cause of infertility, calendar year of treatment, and treatment cycle number (with a multiple logistic regression model), it was found that, relative to human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate, the odds of conceiving with the long buserelin regimen was 1.63 (95% confidence interval 1.31 to 2.03) (p < 0.001) and the odds of a live birth was 1.97 (95% confidence interval 1.53 to 2.54) (p < 0.001). Similarly, relative to short or ultrashort buserelin the odds of conceiving with long bureselin was 1.88 (95% confidence interval 1.39 to 2.55) (p < 0.001) and the odds of a live birth was 1.79 (95% confidence interval 1.25 to 2.56) (p = 0.001). CONCLUSION: Pituitary desensitization with the long protocol of buserelin significantly increases the probabilities of conception and live birth after in vitro fertilization.

Adult↗

Comparison of natural with clomiphene citrate-stimulated cycles in in vitro fertilization: a prospective, randomized trial.

OBJECTIVE: To compare the outcome of natural with clomiphene citrate (CC)-stimulated cycles in IVF. DESIGN: Prospective, randomized study. SETTING: Tertiary referral center for assisted conception. SUBJECTS: Thirty patients randomized to receive either no treatment (n = 14) or CC, 100 mg, from days 2 to 6 (n = 16). INTERVENTIONS: Daily ultrasound (US) scan and measurements of serum LH and E2. Ovarian morphology was assessed on baseline US scan. Human chorionic gonadotrophin was administered when the mean diameter of the dominant follicle reached 17 mm. Transvaginal US-directed oocyte recovery was performed 35 hours later. MAIN OUTCOME MEASURES: The number of patients reaching oocyte recovery; numbers of oocytes collected, fertilized and embryos transferred; and clinical pregnancy and multiple pregnancy rates (PRs) were recorded. RESULTS: Ten cycles in the natural cycle group were abandoned before oocyte recovery compared with none in the CC group. There were significantly more follicles > 14 mm (2.4 +/- 0.3 [SE] compared with 0.9 +/- 0.2) and higher peak levels of E2 (375 +/- 67 pg/mL (1,378 +/- 247 pmol/L) compared with 204 +/- 17 pg/mL (748 +/- 61 pmol/L)) in those receiving CC compared with those receiving no drug. All 16 patients treated with CC had oocyte retrieval (mean, 1.8 +/- 0.3 oocytes) compared with only 4 in the natural cycle group (1 oocyte each). The oocyte recovery rate was 95%. Two patients conceived in the CC group (PR per ET, 18%) compared with none in the natural cycle group. Patients with polycystic ovaries developed more large follicles than those with normal ovaries. No patient developed ovarian hyperstimulation syndrome. CONCLUSIONS: Patients undergoing natural cycle IVF are more likely to have abandoned cycles, produce fewer follicles and oocytes, and are less likely to reach ET than patients treated with CC alone. Clomiphene citrate should be considered for use in the context of a conventionally organised IVF-ET program if a mild degree of ovarian stimulation is desired.

Adult↗

A prospective study comparing unilateral and bilateral laparoscopic ovarian diathermy in women with the polycystic ovary syndrome.

OBJECT: To assess the efficacy of unilateral laparoscopic ovarian diathermy in the induction of ovulation in anti-estrogen-resistant polycystic ovary syndrome (PCOS). DESIGN: A prospective randomized study was performed to compare unilateral with bilateral ovarian diathermy. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS: Ten patients with anti-estrogen-resistant PCOS. INTERVENTIONS: Randomization to unilateral (4 patients) or bilateral laparoscopic ovarian diathermy (6 patients). MAIN OUTCOME MEASURES: Rate and side of ovulation and change in endocrine profiles after ovarian diathermy. RESULTS: Unilateral ovarian diathermy resulted in ovulation from both ovaries. Fifty percent of the patients responded to diathermy and those who responded had a significantly greater fall in serum LH concentrations than those who failed to respond. CONCLUSIONS: The mechanism of action of laparoscopic ovarian diathermy is via a correction of disturbed ovarian-pituitary feedback. Hypersecretion of LH appears to be the most significant endocrine disturbance in these patients.

Adult↗

Cumulative conception and live birth rates after the treatment of anovulatory infertility: safety and efficacy of ovulation induction in 200 patients.

An analysis was performed on the cumulative conception rates, cumulative live birth rates and adverse effects of ovulation induction in patients with anovulatory infertility attending a single unit over an 11-year period. A total of 200 patients were included, 103 with clomiphene-resistant polycystic ovary syndrome (PCOS), 77 with hypogonadotrophic hypogonadism (HH) and 20 with weight-related amenorrhoea (WRA). Ovulation induction was performed using a number of protocols in which pulsatile luteinizing hormone-releasing hormone was administered s.c. or i.v. and gonadotrophins (human menopausal gonadotrophins or follicle-stimulating hormone) were administered i.m. The cumulative conception and live birth rates in the first course of therapy and after 12 cycles of treatment were, respectively, 73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH group and 95.0 and 85.3% in the WRA group. The miscarriage rates for all courses of treatment were 15.5% in PCOS patients, 22.9% in HH patients and 32.3% in WRA patients which resulted in cumulative live birth rates that were not significantly different. The median number of cycles and ovulations to achieve a pregnancy was 2 in all groups. The multiple pregnancy rate was significantly greater in women with PCOS (17.9%) than in women with HH (3.6%, P = 0.0052, 95% CI 5.12-23.36%) but not WRA (3.2%, P = 0.07, 95% CI 4.35-24.92%). The rate of multiple pregnancy fell after the introduction of monitoring by transvaginal ultrasound. Correction of anovulatory infertility by appropriately selected ovulation induction regimens results in cumulative conception and live birth rates indistinguishable from normal.

Amenorrhea↗

Effect of treatment on established osteoporosis in young women with amenorrhoea.

BACKGROUND AND OBJECTIVE: Amenorrhoea in women of reproductive age causes loss of bone mineral. This study assessed the effect of treatment of amenorrhoea on bone mineral density. DESIGN: Serial measurements of bone mineral density were obtained in women receiving treatment for amenorrhoea. PATIENTS: Eighty-five women aged 17-40 with a past or current history of amenorrhoea, from various causes, with median duration of 46.5 months (range 8 months-21 years). MEASUREMENTS: Bone mineral density in the lumbar spine was measured by dual-energy X-ray absorptiometry. RESULTS: Initial vertebral bone mineral density was low, mean 0.85 (SD 0.10) g/cm2. After an interval of 19.6 (SD 7.5) months on treatment there was a highly significant increase to 0.89 (SD 0.10) g/cm2 (P < 0.0005). This was equivalent to a gain in bone mass of 2.1% per year (95% confidence interval 1.5-2.8%). Improvement was seen in all diagnostic groups (except polycystic ovary syndrome) and with all types of therapy. We observed no difference in the response of previously untreated patients compared with those already on treatment, nor any change in response with increasing duration of treatment. No new fractures were reported during the study. CONCLUSIONS: Bone mineral density in young women with amenorrhoea is improved by appropriate treatment, but recovery is not substantial. Hence early diagnosis and therapy is essential to prevent bone loss.

Absorptiometry, Photon↗

Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase.

OBJECTIVE: To review studies that have examined the role of LH, its mechanism of action, and its detrimental effects when hypersecreted during the follicular phase. DESIGN: Important published studies related to this topic were identified through a computerized bibliographic search. PATIENTS, PARTICIPANTS: Review of the need for LH during the follicular phase is based on animal models and women with hypogonadotropic hypogonadism. The association of hypersecretion of LH during the follicular phase with low rates of fertilization and high rates of pregnancy loss is based on clinical studies conducted in patients treated by IVF and ET and by induction of ovulation. The possible mechanism by which the effects occur is based on in vitro studies. RESULTS: The results of the studies cited in this review are consistent with the two-cell two-gonadotropin hypothesis implying that synergistic action of both FSH and LH is required for appropriate steroidogenesis. It also seems that, whatever the underlying mechanism, a raised serum LH concentration during the follicular phase confers a substantial risk of infertility and early pregnancy loss. CONCLUSION: By reviewing the literature it appears that LH exhibits an important role in the development of the growing follicle and maturation of the oocyte. It also seems that hypersecretion of LH during the follicular phase implies adverse effects on the fertility process. To further test this hypothesis, we now need systemic assessment of the methods of therapy used for treating patients with polycystic ovary syndrome, in relation to LH secretion and outcome of pregnancy.

Animals↗

Pneumocystis carinii pneumonia in a term newborn infant with a transiently depressed T lymphocyte count, primarily of cells carrying the CD4 antigen.

A term infant without infection by human immunodeficiency virus had pneumocystis pneumonia at 17 days of life. Initial counts of T lymphocytes carrying the CD4 antigen were approximately 50% of the lower limits of normal; later the counts of T lymphocytes carrying the CD3 and CD8 antigens decreased as well. By 7 weeks after resolution of the pneumonia, CD3+, CD4+ and CD8+ cell counts had returned to normal. These observations suggest that a primary transient deficiency of T cell production or maturation, especially involving CD4+ cells, may occur in otherwise normal newborn infants.

CD4 Antigens↗

A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization.

The outcome of in-vitro fertilization and embryo transfer (IVF-ET) was compared in 76 patients with polycystic ovaries (PCO) diagnosed on pre-treatment ultrasound scan, and 76 control patients who had normal ovaries and were matched for age, cause of infertility and stimulation regimen. Despite receiving significantly less human menopausal gonadotrophin (HMG), patients with PCO, as compared with controls, had significantly higher serum oestradiol levels on the day of human chorionic gonadotrophin administration (5940 +/- 255 versus 4370 +/- 240 pmol/l, P < 0.001), developed more follicles (14.9 +/- 0.7 versus 9.8 +/- 0.6, P < 0.001) and produced more oocytes (9.3 +/- 0.6 versus 6.8 +/- 0.5, P = 0.003). However, fertilization rates were reduced in the PCO patients (52.8 +/- 3.4% versus 66.1 +/- 3.4%, P = 0.007). There was no significant difference in cleavage rates. The pregnancy rate/embryo transfer was 25.4% in the PCO group and 23.0% in the group with normal ovaries. There were three high order multiple pregnancies in the PCO group compared with none in the group with normal ovaries. Of the PCO patients, 10.5% developed moderate/severe ovarian hyperstimulation syndrome (OHSS) compared with none of the controls (P = 0.006). Patients with and without PCO undergoing IVF have comparable pregnancy and livebirth rates. However, it is important to diagnose PCO before ovarian stimulation is initiated as these patients are more likely to develop moderate or severe OHSS following IVF-ET.

Adult↗

Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin.

To assess the risk of miscarriage after in-vitro fertilization (IVF) with respect to age, cause of infertility, ovarian morphology and treatment regimen, a retrospective analysis was performed of the first 1060 pregnancies conceived between June 1984 and July 1990 as a result of 7623 IVF cycles. Superovulation induction was achieved with human menopausal gonadotrophin (HMG) and/or purified follicle stimulating hormone (FSH) together with either clomiphene citrate or the gonadotrophin hormone-releasing hormone (GnRH) agonist buserelin, the latter either as a short 'flare' regimen or as a 'long' regimen to induce pituitary desensitization. There were 282 spontaneous abortions (26.6%) and 54 ectopic pregnancies (5.1%). The mean age of women with ongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2 (SD 4.1) years in those who miscarried, which were significantly different (P = 0.008). There was no relation between the miscarriage rate and the indication for IVF. The miscarriage rate was 23.6% in women with normal ovaries compared with 35.8% in those with polycystic ovaries [P = 0.0038, 95% confidence interval (CI) 4.68-23.10%]. There was no difference in the miscarriage rate between treatment with HMG or FSH. Women whose ovaries were normal on ultrasound were just as likely to miscarry if they were treated with clomiphene or with the long buserelin protocol. Those with polycystic ovaries, however, had a significant reduction in the rate of miscarriage when treated with the long buserelin protocol, 20.3% (15/74), compared with clomiphene citrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82-40.09%).

Abortion, Spontaneous↗