Steve N. London

Ovulation induction with pulsatile gonadotropin-releasing hormone administration in patients with polycystic ovarian syndrome

Gonadotropin-releasing hormone (0.025 microgram/kg) was administered intravenously in a pulsatile fashion to four subjects with polycystic ovary syndrome for a total of six cycles. Five of the six cycles culminated in ovulation, although in one course the response occurred too early to be attributed to the therapy alone. No pregnancies resulted. All luteal phases were of normal duration, but progesterone production as manifested by serum progesterone determination was deficient in some. If additional investigation confirms these preliminary findings, this form of therapy may offer a safe and economic alternative for anovulatory patients refractory to clomiphene citrate therapy. The response of the four subjects suggests that pulsatile gonadotropin-releasing hormone administration may override hypothalamic-pituitary dysfunction and result in ovulatory menstrual cycles.

In vitro fertilization and embryo transfer, Duke University Medical Center

100 mg/day of clomiphene-citrate is administered for 5 days from the fifth day of the menstrual cycle. Ultrasonography and highly sensitive immunoassay of urinary estrogen (Mochida Co., Japan) are used to decide the beginning of urinary LH measurement every 4 hr. We do laparoscopic egg collection 2628 hr after the onset of LH surge or 36-37 hr after HCG injection, depending on the maximum follicular diameter and urinary LH level measured with Hi-Gonavis (Mochida Co.). Incubation is done with Wittinghams T 6 medium including 10% (IM) or 15% (GM) inactivated patients serum under conditions of mixed gas (5% CO2, 5% 02, 90% N2). Six hours after preincubation of the ovum, 3-5 • 10~/ mt of washed sperm is added and incubated for 16 hr of fertilization time. Then the embryo is moved to growing medium and cultured for 36 hr. Fifty-six hours after egg recovery, the embryo is replaced into the uterus with Monash ET Catheter Type 2. Table I. Clinical Results of IVF and ET (February-September 1983, Tohoku University, Sendai)

Macrophages and infertility: enhancement of human macrophage-mediated sperm killing by antisperm antibodies**Supported in part by Veterans Administration grants CA-27070 and CA-10267, awarded by the National Cancer Institute, Department of Health, Education and Welfare, and by the Charles Josiah Trent Foundation.

The mechanism by which antisperm antibodies inhibit fertility is not completely understood. Macrophages may play a role in mediating infertility by interacting with sperm and destroying gametes. Experiments were conducted evaluating the effect of antisperm antibody on the phagocytosis and lysis of sperm by human peritoneal macrophages in vitro. Sperm from a fertile man treated with sera from normal men and women or medium alone had 5 to 280 molecules of IgG/sperm, as determined by a 125I-labeled anti-human IgG monoclonal antibody assay. By contrast, sperm treated with sera containing antisperm antibodies had 310 to 1240 molecules of IgG/sperm. Peritoneal macrophages harvested from infertile women with tubal/adhesive problems mediated phagocytosis and lysis of 111In-labeled sperm which was enhanced by treatment of the sperm with sera containing antisperm antibodies (39.0% +/- 1.5% versus 76.3% +/- 3.2% phagocytosis, and 3.3% +/- 0.3% versus 23.3% +/- 2.3% lysis of sperm [control versus antibody-treated]). The likelihood of fertilization in couples with antisperm antibody may be determined not only by the antibody but also by the presence of genital tract macrophages capable of destroying the antibody-coated sperm.

Diverse humoral and cell-mediated effects of antisperm antibodies on reproduction*†*Supported in part by the Veterans Administration Research Service, grant CA 27070 from the National Cancer Institute, the James Swiger Hematology Research Fund, and the Sarah P. Duke Fund.†Associate Members’ Prize Paper. Presented at the Thirty-Ninth Annual Meeting of The American Fertility Society, April 16 to 20, 1983, San Francisco, California.

No single test to detect the presence of antisperm antibodies has correlated precisely with subsequent fertility. The purpose of this study was to determine whether heterogeneous effects of antibodies could potentially explain this observation. The effects of serum on sperm motility, complement-mediated sperm lysis, mouse macrophage-mediated sperm phagocytosis, and sperm IgG opsonization were assessed in several patients with known antisperm antibodies. Each patients serum produced its own unique profile. Motility ranged from normal (70% to 85%) to 10% using different subjects serum. Antibody-dependent complement-mediated sperm lysis ranged from 35% to 65%. Normal sperm incubated with normal serum had approximately 200 molecules of IgG per sperm, whereas normal sperm incubated with patient sera had 546 to 900 molecules of IgG per sperm. In all cases where serum enhanced IgG sperm opsonization, there was enhanced mouse macrophage-mediated phagocytosis of the opsonized sperm (a three- to fourfold increase). These data suggest that antisperm antibodies may affect reproduction by different mechanisms, including direct humoral effects (immunoglobulin and/or complement) and indirect cell-mediated effects (macrophage-mediated sperm phagocytosis). However, the mechanism(s) involved are unique to each individuals antibody. The heterogeneity of these potential mechanisms may explain why the presence of antisperm antibodies as measured by a single assay correlate poorly with infertility.