Biomedical subjects
Publications and source records attributed to H S Jacobs.
We report a patient with severe psoriatic arthritis in whom the severity of both the arthritis and psoriasis fluctuated with the menstrual cycle. These features failed to improve with standard therapy, but there was a prompt response to treatment which suppressed oestrogen secretion. Such treatment should be considered in patients with disabling cyclical changes in psoriatic arthritis.
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OBJECTIVE: We studied the pretreatment hormone profile and ovarian ultrasound appearance of female-to-male transsexuals. DESIGN: Female-to-male transsexuals who were seen in the local Gender Identity Clinic were examined after psychiatric assessment. RESULTS: Sixteen patients were assessed. Approximately 50% had symptoms and signs of the polycystic ovary syndrome (PCOS) and 15 had a pelvic ultrasound diagnosis of polycystic ovaries. The endocrine profiles of the patients were not markedly abnormal and were compatible with the diagnosis of PCOS. CONCLUSIONS: Polycystic ovaries and the polycystic ovary syndrome are a common finding in female-to-male transsexuals who have had no previous exposure to exogenous androgen therapy.
In the polycystic ovary syndrome, hyperinsulinaemia is commonly found in women with hirsutism, oligomenorrhoea and acanthosis nigricans and this subset of patients possess adverse risk factors for coronary artery disease, particularly reduced HDL2 concentrations. Conversely, raised serum insulin concentrations are not common in women with PCOS in whom raised serum LH concentrations or regular menstrual cycles are present. We postulate that both direct ovarian and indirect actions of insulin (through changes in IGFI-I, IGFBP-I and SHBG concentrations) play important roles in determining androgen concentrations in women. Many intriguing questions follow from this link between the control of nutrition and reproduction and many old observations required re-examination in this new light. Vital to our understanding in this field will be the cause of moderate hyperinsulinaemia, the action of insulin on the normal ovary, and the importance of adverse surrogate risk factors for heart disease in hyperinsulinaemic women.
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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)
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.
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.
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.
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.
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.
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.
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.
Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.
OBJECTIVE: The evidence that some women with the polycystic ovary syndrome (PCOS) are hyperinsulinaemic has brought into question their risk of developing early coronary artery disease. We have focused on three cardiac risk factors which have been associated with hyperinsulinaemia by measuring glucose tolerance, fasting serum lipid concentrations and blood pressure in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in lean and obese women with PCOS and in women with normal ovaries. Determinants of the risk factors for coronary artery disease were assessed by multiple regression analysis. PATIENTS: One hundred and two women with ultrasound diagnosed PCOS and 19 lean women with normal ovaries were studied. Patients were recruited from a reproductive endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides, high density lipoproteins (HDL), HDL2, glucose tolerance, fasting and stimulated insulin, gonadotrophins, testosterone and androstenedione were measured during a 2-hour oral glucose tolerance test. Recumbent blood pressure was measured automatically. RESULTS: Lean women with PCOS were found to be hyperinsulinaemic and have reduced serum HDL and HDL2 concentrations compared to women with normal ovaries; serum insulin concentrations correlated positively with plasma glucose and blood pressure measurements in multiple regression analysis. Obese women with PCOS were in addition found to have higher systolic blood pressure, serum triglyceride and plasma glucose concentration than lean women with PCOS and controls. CONCLUSIONS: These results support the evidence that hyperinsulinaemic women with PCOS have an increased risk of developing cardiovascular disease and therefore form a population in whom metabolic screening is advisable.
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We have explored the use of growth hormone (GH) for ovulation induction and ovarian stimulation for in vitro fertilization and embryo transfer (IVF-ET). We first compared the effects of co-treatment with GH and placebo on the dose of gonadotrophins required to induce ovulation. The patients were gonadotrophin deficient and, for the main part, hypopituitary. We found a significant reduction in the dose of gonadotrophins and the duration of treatment needed to induce ovulation. The dose of GH used in these studies was substantial, and we await the results of a multi-centre trial attempting to establish a dose-response relationship. We then explored the role of GH in patients undergoing IVF-ET. The end-point measured was an increase in the number of follicles developing during standard treatment with gonadotrophins. In the first randomized controlled clinical trial we found a suggestion only of an enhanced ovarian response to co-treatment with GH. Specifically selected patients with ultrasound-diagnosed polycystic ovaries were then treated. All were receiving treatment with luteinizing hormone-releasing hormone analogue as part of their ovarian stimulation protocol. The results showed clearly that in this group of patients, co-treatment with GH augmented the ovarian response to treatment with gonadotrophins. We also found an increase in serum and follicular-fluid insulin-like growth factor I (IGF-I) concentrations, but since the serum concentrations always exceeded those in follicular fluid, the results were consistent with the notion that follicular-fluid growth factor was predominantly derived from serum IGF-I rather than being synthesized locally.