Christine L. Cook

Relationship between serum müllerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women

OBJECTIVE To examine the relationship of serum müllerian-inhibiting substance (MIS), E(2), free-T, LH, and FSH in untreated women with polycystic ovary syndrome (PCOS) and in women with normal menstrual cycles. DESIGN A prospective study. SETTING University Departments of Obstetrics and Gynecology and Surgery. PATIENT(S) Twenty-seven women with PCOS and 20 women with normal menstrual cycles. INTERVENTION(S) Serum was collected from women with PCOS and from normal women during the early follicular phase of the menstrual cycle, stored frozen until assayed. MAIN OUTCOME MEASURE(S) Serum levels of MIS, E(2), free-T, TSH, LH, and FSH were measured. RESULT(S) Serum müllerian-inhibiting substance levels in PCOS patients were significantly higher compared with normal women (+/- SE; 5.3 +/- 0.7 and 1.4 +/- 0.2 ng/mL, respectively). An inverse correlation (r = -0.5965) was found between serum levels of MIS and E(2) in PCOS women, but not in normal women. Women with PCOS had higher serum LH levels than those of normal women (15.2 +/- 1.2 and 5.0 +/- 0.7 mIU/mL). CONCLUSION In this study, women with PCOS have significantly higher serum MIS levels than normal women. The inverse relationship between müllerian-inhibiting substance and E(2) levels suggests that MIS may modulate ovarian E(2) synthesis and have a role in the disordered folliculogenesis characteristic of PCOS.

Serum mullerian-inhibiting substance levels during normal menstrual cycles

OBJECTIVE To measure serum levels of müllerian-inhibiting substance (MIS) during the normal menstrual cycle. DESIGN Serum was collected from women during ovulation and the mid-luteal and early follicular phases of the menstrual cycles. It was stored frozen at -80 degrees C until assayed. SETTING University of Louisville Departments of Obstetrics and Gynecology and Surgery. PATIENT(S) Twenty healthy women 22-35 years of age with normal menstrual cycles. INTERVENTION(S) Blood samples were collected on menstrual cycle day two or three and on the day of LH surge plus one and plus seven or eight. MAIN OUTCOME MEASURE(S) Serum MIS levels were measured by using an enzyme-linked immunosorbent assay. RESULT(S) Serum MIS levels ranged from a low of 1.4 +/- 0.9 ng/mL (mean [+/-SD]) in the early follicular phase, peaked mid-cycle at 1.7 +/- 1.1 ng/mL, and decreased to 1.4 +/- 0.9 ng/mL in the mid-luteal phase of the normal menstrual cycle. CONCLUSION(S) Fluctuations in serum MIS levels during the menstrual cycle suggest that MIS may have a regulatory role in folliculogenesis.

Müllerian-inhibiting substance in follicular fluid and serum: a comparison of patients with tubal factor infertility, polycystic ovary syndrome, and endometriosis

OBJECTIVE To determine Müllerian inhibiting substance (MIS) levels in follicular fluid (FF) and sera of IVF patients. DESIGN Prospective study. SETTING Fertility center. PATIENT(S) Sixty-six patients: 20 with tubal factor infertility, 17 with polycystic ovary syndrome (PCOS), and 29 with endometriosis. INTERVENTION(S) All patients underwent ovarian stimulation with hMG and/or FSH, as well as oocyte retrieval for IVF. MAIN OUTCOME MEASURE(S) Follicular fluid and serum MIS levels and oocyte fertilization rates. RESULT(S) Levels of MIS in FF and sera of PCOS patients were significantly higher than those in tubal factor patients: 7.01 +/- 1.52 versus 1.65 +/- 0.23 ng/mL (mean +/- SE) and 2.97 +/- 0.52 versus 0.92 +/- 0.19 ng/mL, respectively. In endometriosis patients, follicular fluid and serum MIS levels were not significantly different from those in tubal factor patients. In PCOS patients, the percentage of immature oocytes retrieved (17.9% +/- 5.0%) was significantly higher compared with tubal factor (1.5% +/- 1.0%) and endometriosis (9.2% +/- 2.3%) patients. The percentage of oocytes fertilize was significantly lower in PCOS patients (30.2% +/- 5.3%) compared with tubal factor (62.2% +/- 5.5%) and endometriosis (37.5% +/- 5.7%) patients. CONCLUSION(S) Women with PCOS had higher serum and follicular fluid MIS levels, a higher percentage of immature oocytes, and lower fertilization rates than women with endometriosis or pelvic adhesions.

Recurrent pregnancy loss.

This review of recurrent pregnancy loss examines our current understanding of the major etiologies of this unfortunate condition including genetic and endocrine abnormalities, anatomic variations, autoimmune conditions, alloimmune problems, systemic disease, and infection. Diagnostic protocols and treatment strategies are briefly presented. With a high rate of spontaneous normal pregnancy outcome, great care must be taken to do more good than harm.

Alteration of platelet serotonergic mechanisms and monoamine oxidase activity in premenstrual syndrome.

Platelet uptake and content of 5-hydroxytryptamine (5-HT), platelet monoamine oxidase (MAO) activity, and plasma free and total tryptophan levels were determined in patients diagnosed with premenstrual syndrome (PMS) and in control subjects. The Vmax of 5-HT uptake and 5-HT content in platelets of PMS patients were significantly decreased during the premenstrual phase (cycle days -9 to -1) compared to control subjects. Platelet MAO activity was significantly lower postmenstrually (cycle days 5-9) in PMS patients compared to the premenstrual phase. There were no differences in plasma free and total tryptophan levels between PMS patients and control subjects during either interval. As platelets are believed to be a peripheral model for central serotonergic neurons, the results suggest that PMS symptomatology may be related to alterations in serotonergic neuronal mechanisms.

Improved clinical outcomes for in vitro fertilization with delay of embryo transfer from 48 to 72 hours after oocyte retrieval: use of glucose- and phosphate-free media

OBJECTIVE To evaluate clinical outcomes of day 2 versus day 3 ET using a culture media with no glucose or phosphate. DESIGN Retrospective clinical study. SETTING Hospital-based fertility clinic. PATIENT(S) One hundred seventy-six IVF-ET patients undergoing controlled ovarian supraovulation. INTERVENTION(S) IVF and delaying the ET by 1 day. MAIN OUTCOME MEASURE(S) Number of blastomeres per embryo, implantation and pregnancy rates. RESULT(S) Delaying the ET from day 2 to day 3 after oocyte retrieval significantly increased implantation rates (13% versus 24%) and ongoing/delivered pregnancy rates per retrieval (26% versus 44%). Day 3 embryos with > or = 8 blastomeres resulted in a significantly higher pregnancy rate (53%) than day 3 embryos with < 8 cells (23%) and day 2 embryos with > or = 4 cells (31%) or < 4 cells (11%). CONCLUSION(S) Day 3 ET was associated with a significant increase in implantation and pregnancy rates. Delaying the ET until day 3 may permit the selection of more viable embryos than on day 2. The absence of glucose and phosphate from the culture media is compatible with good IVF outcomes.

Induction of luteal phase defect with clomiphene citrate

The effect of clomiphene citrate and progesterone on luteal function in infertile women was studied. Endometrial biopsies were performed in 103 women immediately prior to menstruation. Group 1 (n = 62) had secretory endometrium with a histologic lag time of greater than or equal to 48 hours with respect to the subsequent menses, that is, luteal phase defect. Group 2 (n = 10) had normal histologic characteristics of the secretory phase. Group 3 (n = 31) had anovulatory endometrium. The last group was subdivided into those with polycystic ovary syndrome (n = 9) and those without the characteristic gonadotropin pattern of polycystic ovary syndrome (n = 22). Clomiphene citrate at doses of 50 to 250 mg daily for 5 days was administered for induction of ovulation, timing of ovulation, or treatment of luteal phase defect. An endometrial biopsy was obtained after three ovulatory treatment cycles. Only one fourth of the women with prior luteal phase defect had normalization of the biopsy specimen with clomiphene citrate, while one half of those treated with progesterone had normal specimens. Half of the normally ovulating women had induction of a luteal phase defect with clomiphene citrate. Only women with polycystic ovary syndrome had consistently well-timed endometrial histologic features with clomiphene citrate therapy. Despite successful induction of ovulation, 16 of the other 22 previously anovulatory women had endometrial histologic findings compatible with luteal phase defect. Increasing the clomiphene citrate dosage was unsuccessful in improving endometrial maturation. These results suggest that the use of clomiphene citrate may be associated with a high rate of luteal phase defect induction, except among women with polycystic ovary syndrome. Clomiphene citrate, even at high doses, appears to be ineffective therapy for luteal phase defect.

Plasma gonadotropin and sex steroid hormone levels during early, midfollicular, and midluteal phases of women with luteal phase defects

Thirteen women with luteal phase defects (LPD) confirmed by endometrial biopsies and 14 with histologically normal endometria were studied for early follicular and midfollicular phase follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and for midluteal phase progesterone, estrogen, testosterone, and prolactin levels. The results showed that the women with LPD had significantly lower FSH levels and FSH/LH ratios in the early and midfollicular phases. LH levels, however, were similar in the LPD and normal women. During the midluteal phase, the LPD women showed significantly lower levels of progesterone and estrogen and normal levels of testosterone and prolactin. These findings reaffirm the prevailing concept that events surrounding follicular growth and development can indeed influence the quality of that cycles corpus luteum. Furthermore, LPD as a result of hyperprolactinemia appears to be a different entity from that due to inadequate follicular phase FSH.

Transforming growth factor-α and epidermal growth factor messenger ribonucleic acid and protein levels in human placentas from early, mid, and late gestation

OBJECTIVE Human placenta expresses receptors for transforming growth factor-alpha and epidermal growth factor throughout pregnancy. Experiments were performed to determine whether epidermal growth factor or transforming growth factor-alpha might be synthesized by placental cells and act through an autocrine mechanism to influence functioning of placental cells in vivo. STUDY DESIGN Human placentas from early, mid, and late gestations were analyzed for transforming growth factor-alpha and epidermal growth factor messenger ribonucleic acid and proteins. Polyadenylic acid-positive ribonucleic acid was isolated from placentas from 10, 11, 13, 21, 32, 38, 39, and 40 weeks of gestation and analyzed by Northern analysis for hybridization with complementary deoxyribonucleic acid probes specific for epidermal growth factor or transforming growth factor-alpha. Levels of immunoreactive epidermal growth factor and transforming growth factor-alpha were measured by specific radioimmunoassays in pools of placentas from early, mid, and late gestations, and levels of epidermal growth factor and transforming growth factor-alpha receptor-active protein were measured by radioreceptor assay. RESULTS All placentas had a strong transforming growth factor-alpha hybridization band at 4.5 kb and a weak epidermal growth factor hybridization band at 5.2 kb. High levels of transforming growth factor-alpha immunoreactive protein (90 to 180 ng/mg protein) and low levels of immunoreactive epidermal growth factor (3 to 9 pg/mg protein) were detected in pools of placentas from early, mid, and late gestations. High levels of epidermal growth factor and transforming growth factor-alpha receptor-active protein (250 ng/mg protein) were also detected. CONCLUSION Human placentas contain relatively high levels of immunoreactive and receptor-active transforming growth factor-alpha, as well as transforming growth factor-alpha messenger ribonucleic acid, throughout gestation. This finding suggests that transforming growth factor-alpha may act by an autocrine system to influence human placental cell function in vivo.

Alteration of 5-HT uptake by plasma fractions in the premenstrual syndrome

The effects of plasma and an aqueous plasma fraction from patients with premenstrual syndrome (PMS) and control subjects on the uptake of 5-hydroxytryptamine (5-HT) in washed human platelets and rat forebrain synaptosomes were studied. Pre- and postmenstrual samples of unextracted plasma from the control group significantly enhanced platelet uptake of 5-HT. In contrast, an aqueous fraction following extraction of the plasma with organic solvents caused a dose-dependent decrease of 5-HT uptake. Plasma obtained from patients with PMS caused less stimulation of 5-HT uptake compared to plasma from the control group. The aqueous fraction of premenstrual plasma from patients tended to inhibit 5-HT uptake to a greater extent than a similar plasma fraction from controls. The inhibition of 5-HT uptake was associated with an increase in Km. Aqueous plasma fractions from both groups also inhibited 5-HT uptake in brain synaptosomes. However, there were no significant differences between groups. The results of the platelet study suggest that there may be quantitative differences in the plasma concentration of endogenous factors that affect 5-HT uptake between patients with PMS and control subjects and that such differences may explain the previously reported alteration of platelet 5-HT uptake and content associated with PMS symptoms.