John Jarrell

Treatment-dependent and treatment-independent pregnancy among women with periadnexal adhesions

In an attempt to evaluate the efficacy of salpingoovariolysis we studied 147 women who were found to have periadnexal adhesions on laparoscopic examination. Among these women, 69 were treated by laparotomy and salpingoovariolysis and 78 were not treated. There was no significant difference between the degree of adhesions in the treated group and in the nontreated group. With the use of life table analysis, the cumulative pregnancy rate at 12 and 24 months follow-up was 32% and 45% in the treated group and 11% and 16% in the nontreated group, respectively (p less than 10(-6)). We suggest that although pregnancy might occur in infertile women who have periadnexal adhesions, treatment with salpingoovariolysis is associated with a higher pregnancy rate.

Preliminary characterization of two types of suppressor cells in the human uterus

Survival of the mammalian fetus in an immunologically hostile host has been shown to be determined by the properties of the tissue at the maternal-fetal interface. Suppressor cells have been found in the decidua in both murine and human systems. This study was carried out to further characterize these cells and to determine whether they were present in abnormal early pregnancies and in the endometrium at the time of implantation. Suppressor cells appear in the endometrium after ovulation, and their activity is present in the decidua of successful pregnancies but is absent in missed abortions. Two types of cells have been identified. An early phase large cell appears to be hormone dependent, and later phase small cell appears to be trophoblast dependent. This would suggest that suppressor cells may play a role in protecting the fetal allograft, from the time of implantation, against maternal immunity, thereby allowing a pregnancy to succeed.

A randomized trial of in vitro fertilization versus conventional treatment for infertility

OBJECTIVE To evaluate the effectiveness of IVF in couples with infertility. DESIGN Two hundred forty-five consecutive couples with infertility were randomized to receive one cycle of IVF treatment (experimental group) or to wait for a period of 6 months before receiving IVF treatment, during which time other infertility treatments could have been undertaken (control group). SETTING Patients were referred to the Fertility Clinic at Chedoke-McMaster Hospitals, a university-associated institution in Hamilton, Ontario, Canada, in which IVF has been offered to couples since 1984. PATIENTS Couples with infertility (mean duration of 65 months) not corrected by conventional treatment. They came from all socioeconomic classes, and the costs of IVF treatment, except medication, were covered by the Ontario Health Insurance Plan. MAIN OUTCOME MEASURE Pregnancy was confirmed by ultrasound documentation of a gestational sac or histologic examination of tissue. Outcomes included livebirth, spontaneous abortion, and ectopic pregnancy. The overall pregnancy rate (PR) and the interval-to-pregnancy duration were compared in each group. RESULTS Univariate analysis demonstrated a significant beneficial effect of IVF treatment in patients with bilateral severe tubal disease. Although in other diagnostic categories the crude and cumulative PRs in the experimental group were higher than in the control group, the differences did not reach statistical significance. Among the early IVF group, those with endometriosis had significantly more pregnancies when compared with other diagnostic categories. Although IVF increases the likelihood of pregnancy by 40% with severe tubal disease, the overall 31% increase associated with IVF was not statistically significant. CONCLUSIONS There was a significant difference in favor of treatment in patients with severe bilateral tubal disease. For couples with other causes of infertility, the confidence limits around the treatment effect included unity. To reject the null hypothesis of no treatment effect, a larger sample size or a meta-analysis to combine the results of similar trials is required.

Suppressor cells in human decidua

Decidual suppressor cells have been found in the murine system. These cells are absent at the implantation sites of interspecies mouse embryos which become infiltrated by maternal cytotoxic cells. Suppression is also deficient at the sites of the spontaneous resorption of fetuses in allomated intraspecies pregnancies. This study was carried out to determine whether similar suppressor cells were present in the decidua during successful human allopregnancies. Decidua was obtained from gestations of 13 to 15 weeks and from term gestations, and the lymphocytes were tested for their ability to suppress the response of their peripheral blood lymphocytes to concanavalin A. Eight of eight 13- to 15-week decidual lymphocytes proved to be suppressive. At term seven of twelve lymphocyte preparations at a lower concentration of cells and six of seven at a higher concentration showed suppression. Suppressor cells appear to be present in human decidua and may play a role in preventing maternal immunologic attack on the allogenic embryo, thereby preventing spontaneous abortion.

An analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels☆☆☆

There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

An in vitro fertilization and embryo transfer pilot study: treatment-dependent and treatment-independent pregnancies

A pilot program of in vitro fertilization and embryo transfer at McMaster University is described. Fourteen couples with a clinical diagnosis of infertility due to apparent tubal dysfunction, with evidence of ovulation, and with normal semen analysis underwent induction of superovulation with human menopausal gonadotropin. At laparoscopy, 82 follicles were aspirated and 19 oocytes were recovered. Eleven oocytes demonstrated cleavage and all inseminated oocytes were transferred 49 to 65 1/2 hours after insemination. In vitro fertilization therapy resulted in two pregnancies, one leading to a spontaneous abortion and the other to the birth of a healthy female infant. At 10 to 12 months after in vitro fertilization therapy in the remaining 12 patients, there were three additional pregnancies (treatment-independent), one ectopic and two intrauterine. One patient was delivered of a healthy female infant. In vitro fertilization therapy should be evaluated by a randomized controlled clinical trial.

The effect of medroxyprogesterone acetate (Provera) on ovarian radiosensitivity

Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a radiosensitizing agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44. Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.

Does dihydrotestosterone induce atresia in the hypophysectomized immature female rat treated with pregnant mare's serum gonadotropin?

This study was originally designed to test the hypothesis that the binding of luteinizing hormone in granulosa cells decreases with atresia. The hypophysectomized immature female rat that was primed with pregnant mares serum gonadotropin and treated with dihydrotestosterone was used as a model for atresia. Histochemical analysis of acid phosphatase was used as a marker for atresia and topical autoradiography with iodine 125-labeled human chorionic gonadotropin for binding of luteinizing hormone. Histologically, there was no significant difference in atresia, acid phosphatase, or 125I-labeled human chorionic gonadotropin binding in antral follicles between control animals given pregnant mares serum gonadotropin and animals treated with pregnant mares serum gonadotropin and dihydrotestosterone. Assessment of the total follicular population, however, showed that dihydrotestosterone at dosages of 1 and 5 mg/kg resulted in decreases in atresia of 48% and 58%, respectively. Although these data disprove our hypothesis, they strongly suggest that dihydrotestosterone decreases follicular atresia by increasing the number of small preantral follicles.

Immunoglobulin-mediated hypersensitivity in response to long-term treatment with gonadorelin hydrochloride (Factrel) in a female patient

Recently a patient with severe hypogonadotropic hypogonadism who was given luteinizing hormone-releasing hormone (Factrel) through an infusion pump developed a wheat-and-flare reaction at the sites of injection. Treatment with luteinizing hormone-releasing hormone was discontinued and the immune response was characterized. Skin testing by skin prick test was positive for luteinizing hormone-releasing hormone but negative for vehicle. Radioallergosorbent testing was performed with allergic (patient serum with an elevated serum immunoglobulin E concentration and allergic to inhalant allergens including ragweed pollen) and nonallergic controls. Radioallergosorbent testing was negative for luteinizing hormone-releasing hormone-reactive immunoglobulin E antibodies. Radioimmunoassay of serum of the allergic patient antibody to luteinizing hormone-releasing hormone was positive only for immunoglobulin E. Maximum binding occurred at a dilution of 1:10. Sera from nonallergic and unchallenged patients were negative. It is concluded that this patient developed hypersensitivity reactions caused by IgE antibody to luteinizing hormone-releasing hormone.