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Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 19 recordsLinked to original sources
PubMed1995

Effect of laparoscopic ovarian electrocautery on ovarian response and outcome of treatment with gonadotropins in clomiphene citrate-resistant patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of ovarian electrocautery on the ovarian response to gonadotropic stimulation and pregnancy rate (PR) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS) and high basal serum LH levels. DESIGN: Retrospective study. SETTING: Outpatient infertility clinic in a tertiary referral center. SUBJECTS: Twenty-two women with PCOS, high basal serum LH concentrations, and CC resistance who underwent laparoscopic ovarian electrocautery. Treatment with gonadotropin was scheduled after failure to ovulate spontaneously or conceive after electrocautery. Data from gonadotropin-stimulated cycles were compared with data from treatment cycles in the same patients before ovarian electrocautery. MAIN OUTCOME MEASURES: Number of ampules, duration of induction phase, daily effective dose, PR, and pregnancy outcome. RESULTS: Markedly reduced basal serum LH concentrations and normal menstrual cyclicity in 41% of patients were recorded after laparoscopic ovarian electrocautery. Comparison of gonadotropin-stimulated cycles before and after electrocautery revealed significantly higher rates of ovulation and pregnancy after electrocautery as well as significant reduction in the number of ampules, daily effective dose, and duration of the induction phase with hMG and in daily effective dose with FSH. CONCLUSIONS: Our results indicate an increased ovarian sensitivity to gonadotropins after laparoscopic ovarian electrocautery. A preference for laparoscopic ovarian electrocautery over medical treatment in all or selected groups of CC-resistant PCOS patients is suggested.

Adult↗
PubMed1995

In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests.

The results of in-vitro cervical mucus-sperm penetration tests and cross-hostility tests in 178 couples with repeatedly negative post-coital tests were recorded. Using a protocol of three cycles with intra-uterine inseminations (IUI) followed by three cycles with ovulation induction + IUI, the association between the cause of infertility, results of the in-vitro tests and the outcome of infertility treatment was investigated. We found that repeatedly negative post-coital tests are a good indicator of a cervical mucus-sperm penetration problem. The cross-hostility test clearly differentiates the abnormal factor in this interaction, and a good performance of the donors' spermatozoa in the cervical mucus correlates with increased pregnancy rate. In male factor infertility, failure of the husbands' spermatozoa to penetrate cervical mucus was not indicative of a deficient fertilization potential in vivo. In these patients a serious attempt should therefore be made to reverse the infertility by treatment with IUI or ovulation induction + IUI before attempting assisted reproduction. Women with polycystic ovaries and repeatedly negative post-coital tests should be investigated for sperm receptivity of the cervical mucus. Low receptivity of the cervical mucus may imply that endometrial receptivity and oocyte quality are also low. Ovulation induction and not IUI alone should therefore be used as the preferred mode of treatment to improve pregnancy rate.

Cervix Mucus↗
PubMed1995

Polycystic ovary syndrome: aetiology and management.

Although much clearer ideas concerning therapeutic approaches to patients with polycystic ovary syndrome are developing, the etiology of this enigmatic but common syndrome continues to be a fruitful source of discussion and debate. There is renewed interest in laparoscopic surgical methods of treatment.

Female↗
PubMed1995

Menstrual disturbance and hypersecretion of progesterone in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: While menstrual disturbance is often quoted as a feature of congenital adrenal hyperplasia (CAH), little is known about the mechanism of this symptom. We set out to determine the relationship between menstrual pattern and biochemical characteristics of women with CAH due to 21-hydroxylase deficiency. PATIENTS AND DESIGN: All 21 female patients with classic CAH attending the adult endocrinology clinics at The Middlesex Hospital were reviewed. Their ages at menarche and menstrual pattern were recorded and blood samples were taken in the follicular phase of the menstrual cycle when on their usual maintenance therapy. MEASUREMENTS: Measurements of serum LH, FSH, progesterone, 17 alpha-hydroxyprogesterone, testosterone, androstenedione and plasma renin activity were recorded. Urinary steroid profiles were obtained by gas chromatography and mass spectrometry. Molecular genetic analysis of the 21-hydroxylase gene was performed on leucocyte DNA. RESULTS: In the 18 patients who had spontaneous menarche the degree of menstrual disturbance and progesterone excess was related to the effectiveness of adrenal suppressive therapy. Three out of 21 patients, however, failed to experience menarche on standard medical therapy. These patients with primary amenorrhoea were characterized by reduced endometrial thickening, by non-suppressible serum progesterone concentrations despite suppression of 17 alpha-hydroxyprogesterone levels and by the presence of progesterone metabolites in urinary steroid profiles. Molecular genetic analysis did not differentiate between patients with raised progesterone concentrations and those without. CONCLUSION: A subgroup of women with congenital adrenal hyperplasia have the triad of non-suppressible serum progesterone of adrenal origin, primary amenorrhoea and infertility due to failure of endometrial thickening. The characteristic urinary steroid profile best distinguishes this subgroup of women from others with congenital adrenal hyperplasia and menstrual disturbance due to inadequate adrenal suppression.

17-alpha-Hydroxyprogesterone↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1992

Cumulative conception and livebirth rates after in-vitro fertilisation.

Cumulative conception and livebirth rates related to age and cause of infertility provide the most useful estimate of success after in-vitro fertilisation (IVF), but limited data are available. It is also uncertain whether the probability of pregnancy, livebirth, and pregnancy failure changes with repeated treatment cycles. To assess the effects of patients' age and cause of infertility on these outcomes, we studied the results of 5055 consecutive IVF cycles (773 clinical pregnancies, 518 livebirths) undertaken on 2735 patients in a single IVF unit. Cumulative conception and livebirth rates were analysed by the life-table approach and differences in rates between age-groups and between causes of infertility were measured by the log-rank test and logistic regression modelling. Both conception and livebirth rates per cycle declined with age (p less than 0.001), and cumulative conception and livebirth rates after five treatment cycles were about 54% and 45%, respectively, at 20-34 years, compared with 38.7% and 28.9% at 35-39 years and 20.2% and 14.4% at greater than or equal to 40 years. The two rates were significantly different between causal groups (p less than 0.001 and p = 0.02, respectively) and were lowest in patients with male infertility or multiple infertility factors. The pregnancy failure rate was higher (p = 0.006) in women over the age of 34 years and there was a significant decline in the chances of pregnancy and livebirth per cycle with successive treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Polycystic ovaries as a relative protective factor for bone mineral loss in young women with amenorrhea.

OBJECTIVE: To examine the impact of polycystic ovaries (PCO) on bone mineral density in amenorrheic women of reproductive age. DESIGN: A retrospective analysis and comparison of polycystic ovarian syndrome (PCOS) with non-PCOS amenorrheic women. A subgroup of patients with ultrasound (US)-diagnosed PCO was also investigated. SETTING: Specialist clinic in reproductive endocrinology. PATIENTS, PARTICIPANTS: Six hundred ten consecutive cases, mean age of 29.8 +/- 7.5 years, with current history of amenorrhea of various causes. MAIN OUTCOME MEASURE: Bone mineral density in the lumbar spine (L1 to L4) as measured by dual energy x ray absorptiometry, in relation to PCOS, US-diagnosed PCO, and US findings of normal ovaries. RESULTS: Amenorrheic patients with PCOS were found to be younger (P less than 0.001), with higher body mass index (P less than 0.001), were more estrogenized, as measured by endometrial thickness and uterine cross-sectional area (P less than 0.001), and had higher bone mineral density (P less than 0.001) compared with non-PCOS amenorrheic patients. CONCLUSIONS: Patients with amenorrhea because of PCOS and those with US-diagnosed PCO have a higher bone density compared with amenorrheic patients with normal ovaries as detected by US scan.

Adult↗
PubMed1992

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.

OBJECTIVE: To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle. DESIGN: Prospective randomized study. PATIENTS: Ninety-one patients having their first attempt at IVF. INTERVENTIONS: Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle. RESULTS: The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2. CONCLUSIONS: The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.

Adult↗
PubMed1992

A prospective randomized study of the optimum timing of human chorionic gonadotropin administration after pituitary desensitization in in vitro fertilization.

OBJECTIVE: To determine if there is an optimum time for the administration of human chorionic gonadotropin (hCG) after pituitary desensitization with gonadotropin-releasing hormone agonists (GnRH-a) has been achieved before ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Two hundred forty-seven patients undergoing an IVF treatment cycle who were randomly divided into three groups. INTERVENTIONS: All patients were administered subcutaneously buserelin acetate 500 micrograms/d from day 1 of the menstrual cycle. After pituitary desensitization had been achieved at least 14 days later, ovarian stimulation with human menopausal gonadotropin was commenced. Ovarian stimulation, cycle monitoring, oocyte recovery, and IVF and embryo transfer (ET) techniques were identical in all three groups. Patients in group 1 (n = 79) had hCG administered when the mean diameter of the largest follicle had reached 18 mm, at least two other follicles were greater than 14 mm, and serum estradiol (E2) levels were consistent with the number of follicles observed on ultrasound. Patients in groups 2 (n = 84) and 3 (n = 84) had hCG administered 1 day and 2 days, respectively, after the above criteria had been reached. RESULTS: The mean day of hCG administration (P less than 0.01), maximum serum E2 concentration (P = 0.06), number of days of serum E2 rise (P = 0.03), and mean diameter of the largest follicle (P less than 0.0001) were significantly different. There were, however, no significant differences in the mean number of preovulatory and medium size follicles, number of oocytes recovered or embryos transferred. There were also no significant differences in the oocyte recovery, fertilization and cleavage rates, in the number of embryos frozen, or in the pregnancy rates per initiated cycle and per ET. CONCLUSIONS: There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a.

Adult↗
PubMed1992

Polycystic ovaries in patients with hypogonadotropic hypogonadism: similarity of ovarian response to gonadotropin stimulation in patients with polycystic ovarian syndrome.

OBJECTIVE: To characterize the ovarian response in patients with isolated hypogonadotropic hypogonadism with ultrasound (US) findings of polycystic ovaries (PCO). DESIGN: Twenty-seven treatment cycles in patients with hypogonadotropic hypogonadism and US findings of normal ovaries were compared with 31 cycles in patients with hypogonadotropic hypogonadism and US-diagnosed PCO. Forty-one cycles in the hypogonadotropic hypogonadism and US-diagnosed PCO were compared with 59 cycles of patients with polycystic ovarian syndrome (PCOS) to examine pattern of response after ovulation induction. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic patients in whom 10 had US findings of PCO and 13 patients with PCOS. MAIN OUTCOME MEASURE: Serum estradiol (E2) concentration, number of leading follicles on US, cancellation, and pregnancy rate. RESULTS: Hypogonadotropic patients with US-diagnosed PCO had higher baseline ovarian volume (P less than 0.02) compared with patients with hypogonadotropic hypogonadism with normal ovaries. After ovarian stimulation, a higher mean serum E2 concentration (P less than 0.001), endometrial thickness (P less than 0.001), and increased number of leading follicles (P less than 0.0001) were found in hypogonadotropic patients with US-diagnosed PCO, compared with hypogonadotropic patients with US findings of normal ovaries. Patients with PCOS had a higher serum E2 concentration (P less than 0.008), although they were treated for fewer days (P less than 0.0001) and with fewer ampules of gonadotropin (P less than 0.001) compared with patients with hypogonadotropic hypogonadism with US-diagnosed PCO. CONCLUSIONS: We have characterized a group of hypogonadotropic patients with US findings of PCO, in which the ovarian response to ovulation induction was similar to patients with PCOS. The results have practical and theoretical implications for the etiology and treatment of patients with PCO.

Adult↗
PubMed1992

The administration of glucocorticoids for the prevention of ovarian hyperstimulation syndrome in in vitro fertilization: a prospective randomized study.

OBJECTIVE: To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG). INTERVENTIONS: Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d. RESULTS: The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids. CONCLUSIONS: Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF.

Adult↗
PubMed1992

The role of treatment with growth hormone in infertile patients.

The reality of the interaction of GH and its mediator, IGF-I, with gonadotrophins is now established. The results of these studies and others have obvious implications, both physiologically and clinically. Co-treatment with GH augments the gonadal response to gonadotrophins, and it seems to be of particular value in patients who are poor responders to gonadotrophin treatment and who have pituitary hypofunction induced surgically, idiopathically (hypogonadotrophic hypogonadism) or medically (treatment with GnRH analogues). There is conflicting evidence as to whether the observed effect of GH is exerted directly on the ovary or mediated through IGF-I. Treatment with GH causes a distinct increase in serum IGF-I concentrations, which correlate with, but are always higher than, follicular fluid levels, suggesting that GH stimulates hepatic production of IGF-I and that the effect on the ovary is endocrine. Further research will, hopefully, clearly define the precise therapeutic role of GH in the induction of ovulation, the selection of the most appropriate group of patients to be treated, and the minimum dose of GH needed to sensitize the ovary. Further studies are also needed to explore the action of GH and to define the role of IGF-I in the process of follicular development.

Adult↗
PubMed1992

The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) in the pathogenesis of polycystic ovary syndrome.

The objective of this study was to elucidate the relationship and role of insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), insulin and luteinizing hormone (LH) in the pathogenesis of polycystic ovary syndrome (PCOS). In a pilot study, serum concentrations of IGF-1 were determined in women with PCOS (n = 10), hypopituitarism (n = 12) and normal controls (n = 10). In the main study, serum concentrations of IGF-1, IGFBP-1, insulin and LH in women with anovulation associated (n = 23) and not associated (n = 47) with PCOS were determined. Serum concentrations of IGF-1 were not different in women with PCOS, anovulatory non-PCOS and healthy women but were low in those with hypopituitarism. Mean serum IGFBP-1 in PCOS (33.8 +/- 21.2 micrograms/l) was decreased compared with anovulatory non-PCOS (60.0 +/- 22 micrograms/l) (P = 0.0001), and correlated negatively with insulin concentrations (r = -0.67, P = 0.0006). Patients with PCOS could be separated into those with high LH and those with high insulin levels. It was concluded that women with PCOS have normal serum IGF-1 concentrations but IGFBP-1 levels, regulated by insulin, are low. Hyperinsulinaemia and raised LH are independently capable of stimulating ovarian androgen production. Growth factors may have an important role in the pathogenesis of PCOS.

Adult↗