Gary Holtz

Interleukin-1: a possible role in the infertility associated with endometriosis *

Increased numbers of activated macrophages are associated with mild endometriosis. Interleukin-1 (IL-1) is a protein produced by macrophages and is believed to be a primary mediator of host responses. IL-1 induces prostaglandin and fibrinogen synthesis and stimulates fibroblast proliferation. This study was undertaken to evaluate the role of IL-1 in the infertility associated with mild endometriosis. Peritoneal fluid (PF) was obtained at laparoscopy from 11 patients with minimal or mild endometriosis and from 7 women undergoing tubal ligation. Peritoneal macrophages were isolated and cultured for 24 hours. Peritoneal and macrophage culture fluids were studied for IL-1 activity, which was measured with the EL-4 assay. IL-1 activity was present in the PF of 10 of the 11 patients with endometriosis and 11 of the 11 macrophage culture fluids and was absent in the PF and macrophage culture fluid of the tubal ligation patients. The effect of recombinant alpha-IL-1 on the in vitro growth of 2-cell mouse embryos was also studied. IL-1 in concentrations similar to those present in the PF (greater than 1 U/ml) was toxic to mouse embryo development. We conclude that the IL-1 may play a role in the infertility associated with endometriosis.

An endometrial antibody assay in the clinical diagnosis and management of endometriosis

Coded serum samples from 11 normal fertile men and 17 fertile women without endometriosis (control groups) and 41 women with endometriosis were tested blindly for the presence of endometrial antibodies by use of a passive hemagglutination assay. Endometrial antibodies were either absent or present in low baseline titers in the serum samples from the control group. In contrast, 17 of the 23 (74%) patients with untreated endometriosis had elevated titers of endometrial antibodies in their serum. Of the 18 patients treated with danazol, endometrial antibodies were absent in 7 women who showed a good response at repeat laparoscopy, whereas 4 of 5 women with a poor response had significantly positive titers of antibodies. Six patients treated with danazol did not have repeat laparoscopy, but were found to have endometrial antibody titers in the baseline control range. Endometrial antibody titers in women with a good response to danazol were significantly lower than those in women with untreated endometriosis or with a poor response to danazol (P = 0.003). No correlation was observed between the antibody titers and the stage of endometriosis. The results suggest that the assay for serum endometrial antibodies may prove to be a clinically useful, noninvasive aid in the diagnosis of endometriosis. Sequential determination of endometrial antibody titers may be helpful in assessing the efficacy of pharmacologic therapy for endometriosis and evaluating the cases of patients with possible recurrence of the disease.

Adhesion prevention in the rabbit with sodium carboxymethylcellulose solutions

With the use of a rabbit surgical model, the ability of 1%, 2%, and 3% solutions of sodium carboxymethylcellulose to reduce postoperative uterine adhesions was determined. At all concentrations sodium carboxymethylcellulose was more effective than either 32% dextran 70 or heparinized lactated Ringers solution. Neither the dextran nor Ringers solution had a significant (p less than or equal to 0.05) effect. The beneficial effects of sodium carboxymethylcellulose were closely dose-dependent (correlation coefficient 0.97). Sodium carboxymethylcellulose is highly effective in reducing postoperative adhesions in laboratory animals, and additional studies are warranted to further define its efficacy and safety.

Sperm motility on postcoital testing correlates with male autoimmunity to sperm

To assess whether or not immunologic factors in husbands, wives, or both, influence the motility of sperm in the female reproductive tract, hemagglutination and cytotoxicity sperm antibody (Ab) assays and postcoital tests (PCTs) were performed in 293 infertile couples. More couples without male autoimmunity to sperm (64% of 66; P less than 0.001) had greater than or equal to 10 motile sperm per high power field (adequate PCT), as compared with 26% of 122 couples with untreated male autoimmunity, 19% of 77 couples with corticosteroid-treated male autoimmunity without a pregnancy, and 36% of 28 couples with successfully treated male autoimmunity to sperm. Good correlation was obtained among pregnancy achievement, lack of sperm antibodies, and adequate sperm motility in the PCT (P less than 0.0001). Sperm motility in the PCT correlated positively with sperm motility in the semen and inversely with cytotoxic sperm Ab in the serum and seminal plasma of men and women and hemagglutinating sperm Ab in the cervical mucus samples. Sperm motility in the PCT has a predictive value of 72% for male autoimmunity and 57% for female isoimmunity to sperm in the presence of normal cervical mucus and in the absence of infections.

Effect of Thirty-Two Per Cent Dextran 70 on Peritoneal Adhesion formation and Re-Formation after Lysis *

Thirty-two per cent dextran 70 in dextrose (Hyskon) has been reported effective in limiting adhesion formation following a peritoneal injury when employed in doses larger than that known to be safe for intraperitoneal use in humans. The effectiveness of a lower dosage believed to be safe for human use was investigated. Female rabbits received a standardized injury to their uterine horns and proximal fallopian tubes. Following the injury, Hyskon (2.5 ml/kg of body weight) was dripped over the sites of injury in the treatment group. Animals were reoperated upon 2 weeks later, and adhesions were scored. Hyskon significantly reduced adhesion formation. In a second experiment the effect of Hyskon on adhesion re-formation was evaluated. Adhesions were induced in the same manner. Two weeks later, the animals were reoperated upon, and adhesions were scored and lysed. Hyskon was instilled in the treatment group as in the first experiment. No significant difference was noted between adhesion scores in control and treatment groups after adhesion induction or when re-evaluated 2 weeks after lysis.

Adhesion formation and histologic reaction with polydioxanone and polyglactin suture

A suture material associated with a minimal inflammatory response might be expected to induce less frequent and less severe peritoneal adhesions. A comparison between polydioxanone and polyglactin 910 suture was performed in a rabbit model. Ten sexually mature virgin female New Zealand white rabbits underwent laparotomy and bilateral incisions into the distal uterine cavities. The serosa of the left uterine horn was always reapproximated with polyglactin 910 suture whereas the right uterine horn was repaired with polydioxanone suture. All animals were put to death 28 days later. An adhesion score was given for each uterine horn. Representative sections were obtained for histologic review. Similar histologic responses were found in both groups. No significant difference was noted in adhesion scores between the two sutures. The present study cannot justify the use of one of these sutures over the other with regard to adhesion formation or tissue reaction.

Cytotoxic sperm antibodies and in vitro fertilization of mature oocytes: A preliminary report

The fertilization rates of mature oocytes during in vitro fertilization and embryo transfer (IVF-ET) using fetal cord serum-supplemented insemination media were ⩾57% for five infertile couples without sperm antibodies (group 1). But they were ⩽50% for four of nine infertile couples (group 2) with cytotoxic sperm antibodies in both partners (n=6) or the husband alone (n=3). Two women in group 1 were successful in achieving normal, full-term pregnancies with the delivery of normal infants (χ2=4.2, P < 0.05, by chi-square analysis). One of them consistently tested negative for sperm antibodies, while her husband was previously treated with antibiotics for infection and transient sperm antibodies in the seminal plasma. Subsequently, antibody liters in the husband were in the normal range when the successful IVF-ET was performed. One woman in group 2, with antibodies to her autoimmune husbands sperm but not control sperm and with a long-standing poor postcoital test sperm motility, conceived through artificial insemination with donor sperm (AID) after failing to conceive with her husband through IVF-ET. These data suggest that the presence of cytotoxic sperm antibodies in the serum and/ or secretions of both partners reduces the rates of fertilization of mature oocytes in spite of using fetal cord serum in the IVF media. Pregnancy achievement is impaired in this group.

Plasma Androgens, 17β-estradiol, and sex hormone-binding globulin in patients with hirsutism and/or clitoromegaly

Plasma androgen, 17 beta-estradiol, and sex hormone-binding globulin (SHBG) levels were measured in 11 normal subjects (group 1), 18 hirsute patients with no clitoromegaly (group 2), 13 hirsute patients with clitoromegaly (group 3), and 8 patients with clitoromegaly but no hirsutism (group 4). Significantly elevated levels of testosterone (T) and dihydrotestosterone (DHT) were found in groups 2 and 3 but not in group 4 when compared with group 1. In contrast, levels of dehydroepiandrosterone (DHEA) in groups 1 and 2 were comparable but significantly lower than those in group 3 and 4; the levels in the latter two groups were not significantly different from each other. In groups 2, 3, and 4, levels of androstenedione (delta 4A) and the factor T/SHBG were significantly elevated whereas SHBG levels were significantly suppressed when compared with those of group 1. The clitoral index correlated (P less than 0.01) with DHEA levels in group 3. It is concluded that clitoromegaly without hirsutism is associated with increased plasma levels of DHEA and delta 4A. In contrast, hirsutism without clitoromegaly is associated with elevated levels of T, DHT, and delta 4A but normal DHEA levels.

Isthmic ectopic pregnancy and salpingitis isthmica nodosa

Two hundred eighty-five charts were reviewed from patients who underwent surgery for ectopic pregnancy. Excluded were patients with previous tubal reparative surgery, linear salpingotomy, or failed sterilization. The incidence of isthmic ectopic pregnancy in the remaining 255 cases was 15.3%. The association of salpingitis isthmica nodosa (SIN) and isthmic ectopic pregnancy was determined by review of resected tubal segments. SIN was noted in 17 of 37 cases (45.9%) of isthmic ectopic pregnancy. SIN places the patient at risk for recurrent ectopic pregnancy or infertility. Recommended conservative management of isthmic ectopic pregnancy is segmental resection with postoperative emphasis on documentation of SIN when present. Postoperative hysterosalpingography is recommended with an abnormal contralateral tube or when SIN is noted in the resected tubal segment. Management options after an isthmic ectopic pregnancy when future fertility is desired are presented.