Robert M. Shelden

Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles

OBJECTIVE To test the hypothesis that the concentration of early follicular phase serum müllerian-inhibiting substance (MIS) is associated with ovarian response in women undergoing ovulation induction in preparation for assisted reproductive technology (ART). DESIGN Retrospective analysis of frozen day 3 serum samples. SETTING Academic ART program. PATIENT(S) One sample of frozen day 3 serum from women with < or = 6 retrieved oocytes (n = 28) compared with women with > or = 11 oocytes retrieved (n = 79) in preparation for IVF. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Comparison of day 3 serum MIS levels between two groups of women. Other comparisons included maximum serum E(2) concentrations, number of retrieved oocytes, and percentage of mature oocytes between groups. RESULT(S) Mean serum MIS concentrations were 1.0 +/- 0.4 ng/mL compared with 2.5 +/- 0.3 ng/mL, or more than a 2.5-fold greater serum concentration of MIS in the group with > or = 11 oocytes retrieved compared with in the group with < or = 6 retrieved oocytes. CONCLUSION(S) These data demonstrate an association between early follicular phase serum MIS and the number of retrieved oocytes. Higher day 3 serum MIS concentrations were associated with greater number of retrieved oocytes.

Sexual expression and its determinants in the post-menopausal woman.

Anatomic, hormonal, psychosocial and psychosexual variables of sexual expression were evaluated in 69 non-patient post-menopausal women. Subjects received a 2-h individually administered interview, a gynecologic examination with subjective scoring of vaginal atrophy, and serum determinations of estrone, estradiol, and androstenedione, testosterone, FSH and LH. Sexual repertoire of the 34 coitally active (coitus greater than 3 X monthly) was compared to the 29 coitally inactive (coitus less than 10 X yearly) subjects. The majority of subjects engaged in traditional sexual activities, with emphasis on physical affection and coitus. The active and inactive women were similar on all demographic variables except family income and weight/height ratio. The inactive women were slightly more obese and had lower incomes. Post-menopausal patterns of sexual activity correlated with post-menopausal sexual expression as did partner availability and function. The active women had a significantly higher LH level. No correlation was found between current or ideal sexual frequency and androgen or estrogen levels.

Correlates of sexual desire in post-menopausal women

Sexual desire was studied in 22 post-menopausal women (absence of menses for at least 12 mth) without complaints of sexual dysfunction, not receiving estrogen replacement therapy, and in good physical health. Psychosexual evaluation, medical history, physical and pelvic examinations, and blood samples for the determination of estradiol, androstenedione, FSH and LH were obtained. In addition, the effects of a formal exercise program on sexual desire was investigated. It was found that approximately 50% of the women in this study experienced no decline in sexual interests with menopause, and less than 20% reported a significant decrease. Results indicated a positive relationship between desire and a measure of marital adjustments which women with loss of sex desire had on the Locke-Wallace Marital Adjustment Test. There was no correlation between gonadotropins and loss of sexual desire.

Exogenous gonadotropin requirements are increased in leuprolide suppressed women undergoing ovarian stimulation

We used a subcutaneously administered GnRHa for 21 to 26 days prior to menotropin stimulation, to suppress endogenous LH surges in four patients participating in IVF. GnRHa-pretreated cycles were compared with previous menotropin treatment cycles. Endogenous LH surges were successfully suppressed in all patients. Peak E2 levels and ultrasonographic parameters of follicular development were comparable in the two treatment groups. Exogenous gonadotropin requirements were increased 2- to 4-fold in GnRHa pretreated cycles (P less than 0.05). Ovum recovery rates were not improved by adjuvant LA. These studies indicate that there was an increased ovarian requirement for exogenous gonadotropins as a result of GnRHa therapy. It has to be considered that this may be a direct effect of GnRHa upon the ovary. Alternatively, the absence of endogenous pituitary support in GnRHa-treated patients may account for the increased gonadotropin requirement. Finally, it is possible that this effect is indigenous to this select patient population of poor responders to menotropin stimulation, or to a specific effect of subcutaneously (as opposed to intranasally) administered GnRHa on the ovary. Further studies are needed to clarify the extent to which any or all of these postulated mechanisms may be influencing ovarian response to exogenous gonadotropins after subcutaneous GnRHa pretreatment.

A prospective study on the lack of development of antisperm antibodies in women undergoing intrauterine insemination

To test the hypothesis that intrauterine insemination with washed spermatozoa induces antisperm antibody formation, we measured serum antisperm antibody levels by the Immunobead technique in a population of women receiving exogenous gonadotropins. Antibody levels were measured before therapy (baseline) and then serially during subsequent stimulation cycles, for a maximum of six cycles. Twenty-eight patients underwent intrauterine insemination; each patient served as her own control. An additional 25 patients were treated with exogenous gonadotropins but did not undergo intrauterine insemination; they served as external controls. Antisperm antibody levels in women who underwent concomitant intrauterine insemination were compared with levels in those who did not. Of the 53 enrolled patients, 18 completed six treatment cycles, and 35 achieved pregnancy before six cycles. Forty-five patients (85%) had 25% (28% and 42%, respectively). Mean binding was similar (

Pixe analysis of reproductive fluids.

An external 3.8-MeV proton beam was employed to induce X-rays in 100-mg pellets of human follicular fluids and in 4–8 mg pellets of spermatozoa. The elements Cl, K, Ca, Fe, Cu, Zn, and Br were quantitatively determined in follicular fluids, whereas the elements, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, and Zn were determined in the spermatozoa. Both samples had high interelement Spearman correlation coefficients. Correlations of elements in the samples were observed with several clinical parameters. The multielemental analysis of spermatozoa can be used to approximate quantities of trace elements inserted into the egg ooplasm at the time of fertilization. These elemental quantities appear to be in the femtogram (10−15) range.

Preliminary observations on the collection of baboon oviducal fluid

Five sexually mature and regularly ovulating baboons (Papio cyanocephalus) were subjected to bilateral oviducal cannulation. Prior to failure of the primary cannulation, peri-ovulatory fluids were collected during three menstrual cycles from one animal, during two cycles from a second animal, and during a single cycle from each of two additional animals. These four animals were subsequently recannulated and oviducal fluids obtained during six additional cycles, but tubal fluid collection after the second procedure was generally less satisfactory than following the initial manipulation. Two attempted cannulations in the fifth animal did not result in oviducal fluid collection.Of the 13 menstrual cycles during which tubal fluid was collected, four were apparently anovulatory. Collections from two of these as well as from three ovulatory cycles were characterized by erratic flow and mucous-blood contamination. Tubal fluids were collected without apparent technical interference or serum contamination from six ovulatory and two anovulatory cycles. Maximum volumes (1.77±.34 ml/oviduct/24 hours) of tubal fluids were collected during the 48 hours following the midcycle LH peak. Thereafter, the rate of oviducal fluid collection declined rapidly.

Identification of low and high molecular weight follicle-stimulating hormone receptor-binding inhibitors in human follicular fluid**Supported by training grant DK08236 from the National Institutes of Health, Bethesda, Maryland. ††Presented in part at the 71st Annual Endocrine Society Meeting, Seattle, Washington, June 21 to 24, 1989.

Various fractions of human follicular fluid (FF) were tested for follicle-stimulating hormone (FSH) receptor-binding inhibitory activity, as well as for their ability to form a dansyl derivative previously reported to be associated with FSH receptor-binding inhibitory activity in bovine FF. Pooled human FF was found to inhibit binding of radioiodinated human FSH (125I-hFSH) to its receptor in a concentration-related manner. Fractionation of human FF by sequential ultrafiltration through membranes of calibrated pore size resulted in human FF components of low (500 to 5,000) and high (greater than 5,000) molecular weight, (Mr) respectively. Each of these inhibited 125I-hFSH binding to receptor in a concentration-related manner. Dansylation of the above components revealed the Rf = 0.15 dansyl derivative to be present in unfractionated human FF and in the low (500 to 5,000 Mr), but not the high (greater than 5,000 Mr), component of human FF. These findings are consistent with those previously reported for bovine FF and porcine FF and indicate that human FF contains FSH receptor-binding inhibitors with properties similar to those observed in animal species.