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Biomedical subjects

Z Shoham

Publications and source records attributed to Z Shoham.

At least 19 recordsLinked to original sources

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

BACKGROUND: The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. METHODS: After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. RESULTS: There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. CONCLUSION: In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

Adolescent↗

Sertoli cell tumor causing precocious puberty in a girl with Peutz-Jeghers syndrome.

Distinctive ovarian and cervical tumors are associated with Peutz-Jeghers syndrome (PJS). The most common gynecological tumors in this syndrome are adenoma malignum of the uterine cervix and ovarian sex cord tumor, particularly sex cord tumor with annular tubules (SCTAT). Other kinds of ovarian tumors have been rarely reported in association of PJS, including Sertoli cell tumors. We report a case of a 4.5-year-old girl with PJS who presented with isosexual precocious puberty (IPP) due to ovarian lipid-rich Sertoli cell tumor. In addition to estrinizing effect of the tumor, the patient had decidual reaction secondary to tumor-derived progesterone secretion. The literature on gonadal tumors in PJS is reviewed, including one previous report of ovarian lipid-rich Sertoli cell tumor associated with this syndrome.

Child↗

Prospective evaluation of endometrial thickness as a predictor of pituitary down-regulation after gonadotropin-releasing hormone analogue administration in an in vitro fertilization program.

OBJECTIVE: To determine whether pituitary down-regulation after gonadotropin-releasing hormone analogue (GnRH-a) administration can be accurately predicted by transvaginal ultrasonographic measurement of endometrial thickness. DESIGN: Prospective study. SETTING: An IVF unit of an academic medical center. PATIENT(S): One hundred eighty-one patients undergoing 265 IVF-ET treatment cycles using GnRH-a in the long protocol. MAIN OUTCOME MEASURE(S): Serum concentrations of E2 were determined, and endometrial thickness was measured by transvaginal sonography. The accuracy of endometrial thickness for predicting pituitary down-regulation was calculated. RESULT(S): Pituitary down-regulation, defined as a serum E2 concentration of < or = 55 pg/mL, was achieved in 77% (204 of 265) of the cycles. An endometrial thickness of < or = 6 mm was found in 92.2% (188 of 204) of cycles in which down-regulation was achieved. An estradiol level of < or = 55 pg/mL was present in 95.9% (188 of 196) of cycles with endometrial thickness of < or = 6 mm. CONCLUSION(S): A state of relative hypoestrogenism after GnRH-a administration, indicative of pituitary down-regulation, can be predicted with a high degree of accuracy by ultrasonographic measurement of endometrial thickness. Thus, routine testing for serum E2 concentration may be safely omitted. This may allow further simplification of IVF protocols and increase both cost-effectiveness and patients' convenience.

Adult↗

Acute changes in endometrial thickness after aspiration of functional ovarian cysts.

OBJECTIVE: To evaluate the influence of aspiration of functional ovarian cysts on endometrial thickness. DESIGN: Prospective study. SETTING: An IVF Unit of an academic medical center. PATIENT(S): Twenty-two patients from our IVF program, in whom administration of a gonadotropin-releasing hormone agonist preparation in the "long protocol" failed to induce pituitary desensitization, as evidenced by a serum E2 concentration of >55 pg/mL and the presence of an ovarian cyst of >20 mm in diameter. INTERVENTION(S): Transvaginal ultrasonographic-guided cyst aspiration was performed, and 2 days later, serum E2 concentration and endometrial thickness were reassessed. MAIN OUTCOME MEASURE(S): The values of serum E2 concentration and endometrial thickness before and after cyst aspiration were compared. RESULT(S): Two days after ovarian cyst aspiration, the serum E2 concentration dropped from a mean (+/-SD) of 203 +/- 93 to 37 +/- 34 pg/mL. The mean (+/-SD) endometrial thickness was 9.6 +/- 2.0 mm before cyst aspiration and decreased to 5.9 +/- 2.4 mm after the procedure. CONCLUSION(S): Within 48 hours after ovarian cyst aspiration, a significant reduction in endometrial thickness occurs concomitant with a sharp decline in serum E2 levels. The phenomenon of acute reduction in endometrial thickness in response to acute estrogen withdrawal has not been described previously. The exact mechanism and endometrial component involved in the "shrinking" process should be further investigated.

Adult↗

Ovarian stimulation and in vitro fertilization in women with mature cystic teratomas.

OBJECTIVE: To report the results of ovulation induction and in vitro fertilization-embryo transfer (IVF-ET) in patients with ovarian cystic teratomas. METHODS: Six women with ultrasonographically diagnosed ovarian cystic teratomas (mean diameter 2.4 cm) who presented with infertility underwent IVF-ET (n = 4) or ovulation induction (n = 2). Serial ultrasound examinations were used to determine the size of the cystic teratomas during therapy and throughout pregnancy. RESULTS: Ovarian stimulation was successful, as evidenced by the serum estradiol concentration on the day of hCG administration (mean in IVF-ET patients, 3558+/-1319 pg/mL) and the number of oocytes retrieved (10+/-4.24). Three patients having IVF-ET and both patients having ovulation induction conceived, and six healthy infants were born. Cyst sizes remained unchanged throughout treatment and pregnancy. There were no cyst-related complications during ovulation induction or IVF-ET, or during the entire course of pregnancy, labor, and delivery. CONCLUSION: The presence of ovarian cystic teratoma should not be considered a contraindication for therapy in women undergoing ovulation induction and IVF-ET.

Adult↗

Epithelial ovarian cancer, infertility and induction of ovulation: possible pathogenesis and updated concepts.

Numerous case-control, cohort studies, case reports and reviews have been published during the last 5 years regarding the association between infertility and induction of ovulation and epithelial ovarian cancer. Despite this amount of published material, final conclusions regarding direct linkage between these different aspects of infertility and ovarian cancer, as well as any data relating to a putative pathogenetic mechanism, cannot be drawn. In this review we summarize the available data as well as update a previous review by Shoham published in 1994. We outline some of the information that has become available from basic research which may help to direct investigators to suitable clinical research models that may eventually serve to clarify this enigma. Finally we share ideas that focus on specific high-risk cohorts.

Adult↗

Is hydrosalpinx fluid cytotoxic?

Accumulation of oviductal fluid in the ampullar lumen as a result of occlusion of the infundibulum is referred to as hydrosalpinx. A low pregnancy rate (10%) after in-vitro fertilization (IVF) in hydrosalpinx patients and a relatively high incidence (50%) of abortions during the first trimester suggested that leakage of this fluid into the uterine cavity may exert a cytotoxic effect on the developing embryo. To examine this possibility, we analysed the composition of the hydrosalpinx fluid and tested its effect on human granulosa cells and embryos. Hydrosalpinx fluids and granulosa cells were collected from IVF patients at ovum pick-up. IVF eggs containing three pronuclei (3PN) were employed for this study. Analysis of hydrosalpinx fluids revealed electrolyte concentrations similar to those in serum with lower amounts of total protein and albumin. No blood cells were detected and bacterial cultures were negative. Granulosa cells incubated in hydrosalpinx fluid-containing medium (diluted 1:1) were not morphologically different and showed a steroidogenic capacity that was higher than that of cells incubated in its absence. Fertilized 3PN eggs incubated in IVF culture medium successfully developed into 6- to 8- and 8- to 16-cell embryos within 48 and 72 h, respectively. This rate of embryonal development was not impaired by hydrosalpinx fluid (at either 50 or 100% concentration). In the absence of a demonstrable detrimental effect we suggest that the low implantation rate in hydrosalpinx IVF patients may not be due to an embryotoxic effect. We further suggest that constant passage of fluid into the uterine cavity in these patients could possibly introduce some mechanical interference that may result in implantation failure.

Animals↗

The growth pattern of ovarian dermoid cysts: a prospective study in premenopausal and postmenopausal women.

OBJECTIVE: To evaluate prospectively the evolution of ovarian dermoid cysts and the safety of nonsurgical management in premenopausal women. DESIGN: A prospective study. SETTING: Tertiary hospital-based ultrasonographic unit. PATIENT(S): Between 1985 and 1994, 72 premenopausal and 14 postmenopausal women had ovarian dermoid cysts < 6 cm in diameter diagnosed by ultrasound and were followed up at Kaplan Medical Center in Israel. INTERVENTION(S): Ultrasound examination was scheduled at 3 and 9 months after the initial diagnosis and then annually. Every cyst was measured in three planes. The growth rate of the cysts was calculated from the data gathered. MAIN OUTCOME MEASURE(S): Prospective evaluation of the evolution of dermoid cysts and the safety of nonsurgical management in premenopausal women by an ultrasonographic follow-up. RESULT(S): For the premenopausal and postmenopausal women, the mean age (+/-SD) at diagnosis was 32.3 +/- 8.2 and 61.1 +/- 6.9 years, the mean duration of follow-up was 34.5 +/- 21.6 and 35.3 +/- 26.8 months, the mean cyst size at diagnosis was 3.7 +/- 1.2 and 4.1 +/- 1.5 cm, and the calculated mean growth rate was 1.77 +/- 3.86 and -1.59 +/- 2.48 mm/y, respectively. The difference in the mean growth rate of the cysts between the two groups was statistically significant. The mean growth rate was significantly different from zero in the premenopausal group but not in the postmenopausal group. Twenty-eight women were delivered of 35 healthy infants without complications attributable to the dermoid cysts. The cysts were removed surgically in 24 of the 86 women (27.9%), and benign cystic teratomas were confirmed by histologic examination in all cases. CONCLUSION(S): Premenopausal women with ovarian dermoid cysts of < 6 cm in diameter can be safely managed expectantly, especially if pregnancy is desired. The mean growth rate of dermoid cysts in premenopausal women is 1.8 mm/y.

Adolescent↗

Serum hormone concentrations during treatment with multiple rising doses of recombinant follicle stimulating hormone (Puregon) in men with hypogonadotropic hypogonadism.

OBJECTIVE: To study increases of serum FSH and gonadal response in gonadotropin-deficient men treated with recombinant FSH (Puregon; NV Organon, Oss, The Netherlands). DESIGN: An open, prospective, multiple rising dose study in which volunteers received single daily IM doses of recombinant FSH for 3 weeks. The dose administered was increased at weekly intervals: the first 7 days, 75 IU/d; the subsequent 7 days, 150 IU/d; and the last 7 days, 225 IU/d. PARTICIPANTS: Nine men suffering from isolated gonadotropin deficiency or panhypopituitarism. MAIN OUTCOME MEASUREMENTS: Immunoreactive FSH, LH, inhibin, T, and androstenedione. RESULTS: Serum immunoreactive FSH (median) rose in accordance with the recombinant FSH doses administered from 0.5 mIU/mL (range < 0.05 to 1.9 mIU/mL) at baseline to 4.3 mIU/mL (range 2.0 to 8.5 mIU/mL), 8.4 mIU/mL (range 4.9 to 17.8 mIU/mL), and 13.6 mIU/mL (5.6 to 28.4 mIU/mL) after 1, 2, and 3 weeks of medication, respectively. The elimination half-life of recombinant FSH was 48 +/- 5 hours (mean +/- SD), which was slightly longer than that reported after single dose administration of recombinant FSH (32 +/- 12 hours). The bioactivity of recombinant FSH was reflected by serum inhibin levels, which rose from 116 U/L (range 34 to 356 U/L) at baseline to 350 U/L (range 63 to 1,109 U/L) at day 22. However, serum FSH and inhibin levels did not correlate when compared after 1, 2, and 3 weeks of recombinant FSH administration. Serum immunoreactive LH, T, androstenedione, and E2 were 0.2 mIU/mL (range < 0.05 to 0.7 mIU/mL [conversion factor to SI unit, 1.0]), 58 ng/dL (range < 12 to 222 ng/dL [conversion factor to SI unit, 0.0347]), 14 ng/dL (range 6 to 115 ng/dL [conversion factor to SI unit, 0.0349]), and 14 pg/mL (range < 14 to 16 pg/mL [conversion factor to SI unit, 3.67]), respectively, at baseline and remained unchanged during the entire treatment period. CONCLUSION: These data indicate that recombinant FSH treatment increases serum FSH in a dose-proportional fashion, increases inhibin secretion, and lacks intrinsic LH activity.

Adult↗

Estrogen biosynthesis--regulation, action, remote effects, and value of monitoring in ovarian stimulation cycles.

OBJECTIVE: To review current knowledge regarding estrogen biosynthesis, its regulation and action, specifically concerning local as opposed to remote effects of this hormone, and to examine the effectiveness and prognostic value of monitoring hormone concentrations and endometrial response in cycles of controlled ovarian hyperstimulation. DATA IDENTIFICATION AND SELECTION: Studied that relate specifically to estrogen biosynthesis, enzymatic pathways, estrogen receptor physiology, and the clinical aspects of estrogen monitoring were identified through literature and Medline searches. RESULTS: Folliculogenesis is the basic unit of ovarian activity, which has a dual purpose: oocyte maturation and steroid production. Steroidogenic granulosa and theca cells cooperate under gonadotropin control to produced estrogens by stimulating synthesis of steroidogenic enzyme messenger RNAs. Steroid synthesis is amplified further by local growth factors and follicular cell multiplication. Estrogen synthesis is directed by FSH, and only small amounts of LH are needed to amplify the follicular estrogenic potential. However, the growth of preovulatory follicles can proceed without LH, under FSH regulation only, even in the presence of low peripheral estrogen levels. Oocyte maturation and fertilization may proceed independently of ambient estrogen levels, leading to the assumption that estrogen exerts a minimal autocrine-paracrine function. The notable effect of follicular estrogen production is to promote adequate receptive endometrium for embryo implantation. Clinical treatment cycles may be monitored more effectively by evaluating end-organ response to estrogen rather than by evaluating absolute serum E2 concentrations or sonographic follicular measurements. CONCLUSION: Follicular estrogen production is regulated by a complex set of signals that synergize to produce optimal steroidogenesis. Most importantly, the effect of estrogen is truly an endocrine effect, as it prepares the endometrium for implantation. Therefore, the goal of effective treatment and monitoring strategies should focus on direct assessment of the biologic activity of estrogen as it optimizes endometrial receptivity in anticipation of subsequent implantation.

Animals↗

Recombinant technique and gonadotropins production: new era in reproductive medicine.

OBJECTIVE: To review current knowledge regarding recombinant DNA technology and its safety and efficacy in relation to recombinant gonadotropin production. DATA IDENTIFICATION AND SELECTION: Studies that relate specifically to recombinant DNA technology, method of laboratory production, and the clinical aspects of using recombinant gonadotropins were identified through literature and Medline searches. RESULTS: Recent developments in recombinant DNA technology have resulted in a rapidly expanding range of new diagnostic and therapeutic opportunities. This technology paves the way to the identification, isolation, cloning, and production of specific proteins. Recently, recombinant human gonadotropins became available for clinical use. The pharmacokinetics, receptor availability, pharmacodynamics, and safety were studied extensively and the drugs were found to be identical if not superior to urinary gonadotropins that have been used in reproductive medicine for the last 30 years. It is clear today that the use of recombinant human gonadotropins is expected to provide better batch-to-batch consistency, steady supply, and most importantly, a purified compound with high specific activity, which accounts for >99% of the preparation's protein content, allowing SC administration. CONCLUSION: There is no doubt that recombinant gonadotropins produced by genetic engineering technology are here to stay and will represent an important treatment modality in various fertility disturbances.

Clinical Trials as Topic↗

Recovery of corpus luteum function after prolonged deprivation from gonadotrophin stimulation.

Three women with hypogonadotrophic hypogonadism, all desiring pregnancy, participated in a prospective open study attempting to assess the ability of the human corpus luteum to recover after 7 days of deprivation from gonadotrophin stimulation. Follicular growth was induced by gonadotrophins. An endogenous luteinizing hormone (LH) surge was induced by the s.c. injection of a gonadotrophin-releasing hormone agonist. For luteal support, 10 mg/day oral medroxyprogesterone acetate were given for 7 days, after which a single i.m. injection of human chorionic gonadotrophin (HCG) was administered. Monitoring during the follicular phase consisted of daily measurements of serum oestradiol, LH and follicle stimulating hormone (FSH) concentrations, and of follicular growth by transvaginal ultrasonography. During the luteal phase, monitoring consisted of measurements of serum concentrations of LH, FSH, oestradiol, progesterone, 17-hydroxyprogesterone and beta-HCG. Ovulation and luteinization occurred in two patients, demonstrated by transient marked increases in serum progesterone and 17-hydroxyprogesterone concentrations which decreased to basal preovulatory values and increased again following the administration of HCG 7 days later. In the third patient, ovulation and luteinization did not occur, and the subsequent administration of HCG did not result in an increase in progesterone concentration. Of the two patients who ovulated, one conceived and the second had a luteal phase of 15 days duration. Our preliminary results suggest that the human corpus luteum can be 'rescued' and can function normally after 7 days of deprivation from gonadotrophin stimulation in patients with hypogonadotrophic hypogonadism.

17-alpha-Hydroxyprogesterone↗