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Biomedical subjects

V M Sopelak

Publications and source records attributed to V M Sopelak.

At least 19 recordsLinked to original sources

Ovarian endometriomas do not adversely affect pregnancy success following treatment with in vitro fertilization.

PURPOSE: Ovarian endometriomas have an uncertain impact on outcome following in vitro fertilization (IVF). Some authors describe a poor response to ovulation induction, and others observe decreased pregnancy success rates. Conversely, IVF outcomes similar to those of patients undergoing IVF for tubal-factor infertility have also been reported. To determine the impact of ovarian endometriomas on pregnancy success in our IVF program, we identified patients with endometriosis and compared outcomes that were stratified by the presence or absence of an endometrioma at the time of follicular aspiration. METHODS: One hundred eight patients with a diagnosis of endometriosis treated with IVF were identified, retrospectively. In this group, 24 patients completed 29 cycles in which an ovarian endometrioma was aspirated at the time of oocyte retrieval, and 84 patients without endometriomas completed 147 cycles. The cycles from these two groups were compared for differences in peak estradiol, number of mature follicles, number of oocytes, number of embryos transferred, and clinical pregnancies. RESULTS: There were no significant differences between the two groups with respect to peak estradiol, mature follicles, number of oocytes, number of embryos transferred, or clinical pregnancies. CONCLUSIONS: From this retrospective observational analysis it appears that aspiration of an endometrioma at the time of oocyte retrieval has no adverse effect on outcome. This information may prove helpful when faced with the decision to cancel an IVF treatment cycle in patients with this uncommon complication.

Adult↗

Elevated luteinizing hormone on the day of human chorionic gonadotropin administration does not reduce cycle fecundity in a low-dose flare-up in vitro fertilization protocol.

OBJECTIVE: To determine if elevated LH at the time of hCG administration occurs and adversely affects success in a low-dose gonadotropin-releasing hormone analogue (GnRH-a) flare-up protocol in hMG-stimulated IVF cycles. DESIGN: Pearson correlation matrix analysis of hormonal, gamete, and clinical data derived from 203 consecutive IVF cycles was performed. All patients were treated with low-dose GnRH-a (250 micrograms SC leuprolide acetate) and hMG. In 203 consecutive IVF cases, serum was obtained on the day of hCG administration and assayed for E2, LH, and P. These data were correlated with peak E2, number of follicles, oocytes, embryos, and conceptions. Additionally, patients with elevated LH were compared with the nonelevated LH group. RESULTS: Twenty six women had LH > 35 mIU/mL (mean +/- SEM; 51.1 +/- 1.9) and five pregnancies (cycle fecundity 19.2% per retrieval). One hundred seventy-seven patients had LH < 35 mIU/mL (16.3 +/- 0.5) and 25 pregnancies (cycle fecundity 14.1%). There were no differences in the mean P (1.0 +/- 0.1 ng/mL, conversion factor to SI unit, 3.81) and E2 (1,672 +/- 144 pg/mL, conversion factor to SI unit, 3.671) of the former group compared with the P (1.1 +/- 0.07 ng/mL) and E2 (1,456 +/- 69 pg/mL) of the latter group. There was no correlation with the number of follicles, oocytes, embryos, pregnancies, E2, or P to LH concentration (rmax = 0.132). CONCLUSION: In a low-dose, GnRH-suppression, IVF induction protocol, elevated LH occurs in a small subset (13%) of women at the time of hCG administration. This event does not appear to alter cycle fecundity nor induce premature luteinization.

Chorionic Gonadotropin↗

Luteal phase consequences of low-dose gonadotropin-releasing hormone agonist therapy in nonluteal-supported in vitro fertilization cycles.

OBJECTIVE: To determine the follicular and luteal phase impact of low-dose GnRH agonist (GnRH-a) treatment during follicular stimulation for IVF. DESIGN: A randomized prospective study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate (CC) and hMG cycles. SETTING: Patients were treated through a university-based IVF-ET program. PATIENTS: Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG. RESULTS: Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy; however, there was no statistically significant difference in luteal P levels. Follicular parameters were the same (peak E2, number of follicles, and number of oocytes), suggesting that folliculogenesis was not altered. There were no statistical differences in pregnancy rates. CONCLUSIONS: Sustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function.

Clomiphene↗

Regulation of early gestational corpus luteum function in spontaneous and follicular stimulated conceptions.

OBJECTIVE: To determine the regulatory role of hCG on P secretion in normal and abnormal (abortive and ectopic) first trimester pregnancies. STUDY DESIGN: The number of doublings of hCG per day (1/DT; reciprocal of hCG doubling time) was correlated with serum P using linear and nonlinear models in normal intrauterine pregnancies, spontaneous abortions, and ectopic pregnancies (EPs) conceived spontaneously or after clomiphene citrate (CC). RESULTS: Linear correlations between P and 1/DTs of hCG were poor. In contrast, nonlinear modeling with a hyperbolic curve fit the data well and allowed all of the data to be included for analysis regardless of the pregnancy type. Furthermore, this model could be used to explain the differential P concentrations seen in normal and abnormal first trimester pregnancies. The nonlinear hyperbolic model demonstrated that follicular events determine the maximal P production during early gestation. Human chorionic gonadotropin 1/DTs approximately equal to 0.5 sustain maximal P production. Progesterone production is then sustained by the rate of change of hCG. CONCLUSION: Nonlinear correlation analysis suggests that P production in early gestations is regulated by prior follicular events and the rate of hCG production.

Abortion, Spontaneous↗

Bromocriptine inhibition of anesthesia-induced hyperprolactinemia: effect on serum and follicular fluid hormones, oocyte fertilization, and embryo cleavage rates during in vitro fertilization.

Thirty-two patients undergoing in vitro fertilization (IVF) were given bromocriptine either 1 or 12 hours before anesthesia or received no drug to determine what effect suppression of transient, anesthesia-induced hyperprolactinemia would have on peripheral and follicular fluid hormones, fertilization and cleavage rates, and pregnancy. Thirty minutes after anesthesia, there was a 120-ng/mL rise in serum prolactin (PRL) in control patients versus an insignificant change in women given bromocriptine. Levels of PRL in follicular fluid were significantly less, and estradiol (E2) levels were higher (P less than 0.05) in all bromocriptine-treated patients compared with controls, whereas follicular fluid levels of progesterone (P), inhibin activity, and midluteal serum P were unaffected. Although fertilization and pregnancy rates were similar, a greater proportion of fertilized oocytes from bromocriptine-treated patients advanced to cleaving embryos compared with controls (95% versus 63%, respectively; P less than 0.001). We conclude that bromocriptine, given before anesthesia, can suppress transient, anesthesia-induced hyperprolactinemia and dramatically alter follicular fluid concentrations of PRL and E2. Although these changes in hormonal milieu affected neither oocyte fertilization nor pregnancy rate in our IVF patients, they seemed to have a positive influence on embryonic development after IVF.

Adult↗

Failed fertilization during an in vitro fertilization cycle after oral ingestion of amantadine hydrochloride.

Oocyte fertilization occurred during three in vitro fertilization/embryo transfer (IVF/ET) treatment cycles of an infertile couple but failed during an IVF cycle when the husband took amantadine for prophylaxis against viral infection. Semen parameters were similar to those of other cycles attempted by this couple as well as to those of other IVF couples treated concurrently. We circumstantially suggest that amantadine, and potentially other ingestible medications or foods, while not spermicidal, may impair gamete function during IVF/ET.

Adult↗

Infusion of gonadotropin-releasing hormone agonist during pregnancy: maternal and fetal responses in primates.

To determine whether a gonadotropin-releasing hormone agonist could cross the placenta to the fetus, each pregnant rhesus monkey (110 to 155 days' gestation, n = 10) and her in utero fetus had indwelling cannulas placed in the femoral veins. Gonadotropin-releasing hormone agonist (1000 micrograms intravenously) was injected into the mother (n = 8) or fetus (n = 2); serial blood samples were collected from mother and fetus for luteinizing hormone and follicle-stimulating hormone determination. None of the mothers responded to the gonadotropin-releasing hormone agonist bolus. In contrast, some of the fetal monkeys receiving gonadotropin-releasing hormone agonist via placental transfer and all fetal monkeys injected directly with the agonist responded as indicated by increased luteinizing hormone (2.8- to 12.3-fold) and follicle-stimulating hormone (1.5- to 8.9-fold) concentrations. In evaluating maternal and fetal effects, we found that continuous maternal infusion with either gonadotropin-releasing hormone agonist (n = 14) or saline solution (n = 11) throughout pregnancy did not alter maternal hormonal profiles. Histologically, gonads from their infants, removed within 3 days post partum, were normal. Although neonatal ovarian weights were unaffected by the in utero treatment, the testes weighed less (p less than 0.05) in male infants born of mothers treated with gonadotropin-releasing hormone agonist compared to controls. Thus gonadotropin-releasing hormone agonist can cross from maternal to fetal circulation, and the fetus can respond (at least during the third trimester).

Animals↗

Role of transmigration and abnormal embryogenesis in ectopic pregnancy.

Transmigration of ovum and/or sperm may occur, as deduced by the presence of EP in the fallopian tube contralateral to the corpus luteum. The frequency of occurrence of transmigration is relatively low, and, in many cases, other routes of ovum and sperm transport (i.e., intrauterine migration, tubal recanalization, fistula formation) may lead to the ectopic implantation site. In our view, the percentage of abnormal embryos associated with EP is no different from those associated with spontaneous abortions of intrauterine origin. Embryos from spontaneous abortions-of either intrauterine or extrauterine origin-seem to have more abnormalities than embryos from induced abortions. Other etiologic factors such as tubal disease, strictures of the fallopian tube, or endocrinopathies seem to contribute more significantly to the incidence of EP than does abnormal embryogenesis.

Abdomen↗

Follicular stimulation versus ovulation induction in juvenile primates: importance of gonadotropin-releasing hormone dose.

We evaluated the dose of GnRH administered by 1-min pulsatile infusion necessary to achieve follicle growth vs. the dose needed for ovulation induction. Doses of 6.0, 0.6, and 0.06 micrograms GnRH were given to juvenile monkeys iv in 1 min once per h for 4 consecutive months. Monkeys receiving hourly 6.0-micrograms doses of GnRH had cyclic elevations of serum estradiol and had menses, but did not ovulate, as evidenced by lack of a corpus luteum at laparoscopy and consistently low progesterone concentrations. These monkeys ovulated only when hCG was administered near midcycle as a surrogate LH surge. In contrast, monkeys receiving 0.6-microgram doses of GnRH frequently had normal ovulatory menstrual cycles and characteristic elevations of progesterone during the luteal phase. Typically, juvenile monkeys receiving hourly 0.06-microgram doses of GnRH initially had development of a dominant follicle contemporaneous with a rise of serum estradiol, but never ovulated or had any subsequent follicular growth or elevated steroidogenic activity. In summary, ovarian follicular development and steroidogenesis in juvenile monkeys can be initiated by doses of GnRH ranging from 0.06-6.0 micrograms/h, although spontaneous ovulation and normal luteal function occurred frequently only with the 0.6 micrograms/h pulses of GnRH. Thus, the dose range of pulsatile GnRH needed for follicle growth is much broader than that required for induction of ovulatory menstrual cycles.

Animals↗

Prevention of gonadotropin-releasing hormone antagonist induced luteal regression by concurrent exogenous pulsatile gonadotropin administration in monkeys.

We studied the effects of a gonadotropin-releasing hormone (GnRH) antagonist given in midluteal phase. Monkeys received the antagonist (n = 6), [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-GnRH: hydrochloride or vehicle (n = 5). Absent luteinizing hormone (LH) pulsatility, diminished progesterone (P) secretion (P less than 0.01), luteal phase truncation and premature menstruation were observed in all receiving the antagonist. To investigate the site of action, four females received pulsatile exogenous human menopausal gonadotropins (hMG) concurrently, whereby P secretion was sustained and premature menstruation was averted. Equivalent treatment using "pure" FSH, failed to sustain P levels and timely menstruation occurred, confirming the continuing dependence of the corpus luteum on LH. The antagonist acts by central suppression and in turn, diminishes P biosynthesis. LH is luteotropic, since pulsatile LH (hMG), not "pure" FSH, prevented luteolysis.

Animals↗

Blockade of the estrogen-induced luteinizing hormone surge in monkeys: a nonsteroidal, antigenic factor in porcine follicular fluid.

That both follicular fluid extracts and ovarian hyperstimulation block estrogen-induced gonadotropin surges in primates has been established. In the present study, the differential actions of gonadotropin-releasing hormone (GnRH) and estradiol benzoate (E2B) on bioassayable LH (BIO-LH) secretion in the presence of a porcine follicular fluid (pFF) extract were assessed. Further, the inherent immunogenicity of the follicular fluid factor(s) that block estrogen-induced surges was examined. In castrated monkeys, administration of Florisil/charcoal-extracted pFF did not affect BIO-LH secretion induced by exogenous GnRH, although the pFF extract abolished E2B-induced BIO-LH surges. In monkeys given pFF chronically (for 6 to 8 months), immune responses capable of neutralizing the inhibitory actions of pFF on the E2B-induced BIO-LH surges developed. In these pFF-immunized monkeys, the BIO-LH surge induced by an E2B challenge was restored despite concurrent pFF injections.

Animals↗

Contralateral tubal-ovarian apposition and fertility in hemiovariectomized primates.

Here, we examined longitudinally (1) the incidence of pregnancy in hemiovariectomized macaques possessing only one ovary contralateral to a single fallopian tube, i.e., pregnancy after transabdominal ovum migration; (2) the pregnancy rate after surgically achieving contralateral apposition of the ovary and fallopian tube; and (3) the frequency of ovulatory menstrual cycles, patterns of menstruation, and steroid profiles in serum of intact versus hemiovariectomized monkeys to determine whether the ovarian cycle is altered by constraining recurrent follicular maturation and corpus luteum function to one ovary. Despite matings during 28 ovulatory menstrual cycles, none of the five primates possessing only one ovary contralateral to a single fallopian tube became pregnant. In contrast, following contralateral tubal-ovarian apposition, three of these five monkeys conceived after only nine ovulatory menstrual cycles. Hemiovariectomy of monkeys did not compromise the regularity of menstrual cycles or frequency of ovulation, compared with intact control females over the 13-month interval of study (P greater than 0.01). Thus, tubal-ovarian apposition is required in these primates for efficient ovum pickup and fertilization and deserves further clinical scrutiny for women having one functional ovary and one healthy fallopian tube, albeit contralateral.

Animals↗

Transitory increases of luteinizing hormone and follicle-stimulating hormone following luteectomy in hemiovariectomized primates significantly increase progesterone secretion in vitro by the subsequent corpus luteum.

Ten chronically hemiovariectomized cynomolgus and rhesus monkeys were luteectomized 5.5 +/- 0.3 days after the midcycle luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surge in two consecutive cycles. The corpus luteum (CL) was removed, weighed, dispersed with collagenase and the luteal cells counted. Luteal cells (50,000/ml) were incubated in Ham's F10 medium for 3 h at 37 degrees C either in the presence or absence of 100 ng/ml human chorionic gonadotropin (hCG). Daily blood samples were taken from the monkeys throughout the study for determination of LH, FSH, estradiol (E2) and progesterone levels. Within 5 days following each luteectomy (LX), all monkeys responded with a significant increase in FSH and LH (P less than 0.05). Ovulatory LH/FSH surges occurred 14.4 +/- 0.5 days after the first LX. Hormonal profiles of serum progesterone prior to the first and second LX, CL weight and number of luteal cells/CL were similar (P greater than 0.05). However, luteal cells obtained at the second LX produced more progesterone (P less than 0.05) in vitro under basal and hCG-stimulated conditions than cells from the first LX. The areas under the LH and FSH curves following the first LX were highly correlated (P less than 0.05) with the in vitro progesterone production following the second LX. Thus, the monkeys with the largest areas under the LH and FSH curves subsequently had the highest in vitro progesterone production.

Animals↗

Maintenance of ovulatory menstrual cycles in chronically cannulated monkeys: a vest and mobile tether assembly.

We report maintenance of apparently normal ovulatory menstrual cycles in cynomolgus monkeys up to 3 months after their placement in a vest and mobile tether assembly, with or without chronic cannulation via a femoral to vena caval catheter. Since menstrual cyclicity and characteristic hormonal profiles of the principal ovarian steroids remained normal in these monkeys, use of the vest and mobile tether apparatus described here permits long-term study of the hypothalamic-pituitary-ovarian axis during chronic cannulation without introducing overt aberrancies as a part of the experimental model.

Animals↗