Tubal pregnancy with normal hysterosalpingogram and negative serum pregnancy test.

A patient undergoing evaluation for primary infertility with regular menses had a normal hysterosalpingogram in the follicular phase and underwent diagnostic laparoscopy the next day, with the finding of a tubal pregnancy. The patient had a negative serum pregnancy test. Although a normal hysterosalpingogram and negative serum pregnancy test are each rare with a tubal pregnancy, the combination of the two occurring in a tubal pregnancy is previously unreported and did not exclude the diagnosis in this case.

Genetics studies in incomplete müllerian fusion.

No formal genetic studies of incomplete müllerian fusion anomalies have been conducted previously, despite several reports of familial aggregates. Accordingly, the authors sought to determine the frequency with which symptomatic müllerian fusion anomalies occurred in relatives of a small but genetically unbiased sample of 24 probands. Only one of 37 (2.7%) female sibs over age 16 appeared to have a symptomatic uterine anomaly; none of 24 mothers, none of 45 maternal aunts, and none of 50 paternal aunts appeared affected. Such a low frequency of affected relatives is more consistent with polygenic/multifactorial etiology than with other genetic etiologies.

Conservative surgery for endometriosis in the infertile female: a study of 206 patients with implications for both medical and surgical therapy.

Two hundred and six women with endometriosis classified as mild (88), moderate (50), or severe (68) were evaluated after conservtive surgery. The duration of infertility was not related to the severity of the condition. In 137 patients, endometriosis was the only known cause of the infertility. Pregnancy rates in this group were 73.2%, 55.9%, and 40.4%, respectively, for patients with mild, moderate, and severe endometriosis. Of 56 patients with mild endometriosis (peritoneal involvement only), 78.0% had been infertile for 2 or more years; 73.2% became pregnant. These facts suggest that endometriosis, even in its mild form, does interfere with the conception process and that, in some way, surgery is efficacious. The surgery was most beneficial in the early postoperative period. Of patients who conceived, 30.5% did so within 3 months, 48.8% within 6 months, and 86.0% within 15 months after surgery. The data suggest that if medical suppressive therapy is to be used in conjunction with conservative surgery to enhance fertility, it should be used preoperatively rather than postoperatively.

Surgical treatment of endometriosis in the infertile female: a modified approach.

Two groups of infertile women underwent conservative surgery for endometriosis, group I (107 patients) prior to 1970 and group II (138 patients) after 1970. To determine whether modifications to the surgical approach after 1970 further increased the likelihood of conception, postoperative pregnancy rates were examined. The data suggest that postoperative pregnancy rates can be improved by (1) removal rather than "repair" of diseased adnexa if the involvement is unilateral and (2) leaving diseased areas undisturbed where excision or cauterization may predispose to the development of postoperative ovarian and/or tubal adhesions. The current surgical technique (used for group II) is described in detail.

Cyclic use of combination oral contraceptives and the severity of endometriosis.

PIP: The author reports on 206 cases of endometriosis examined between 1970-1977. 172 patients had used OC (oral contraception) for a varying period of time prior to diagnosis of endometriosis; of these, 122 had taken only combined OCs containing 50 mg. or more of estrogen. These data neither support nor contradict the contention that the cyclic use of the combination pill will alter the progression of endometriosis. The only difference within the groups with mild, moderate, or severe endometriosis was the length of treatment. Endometriosis can cause infertility as well as other problems; if the dose of estrogen plays a role in the etiology of endometriosis, low-dose combination pill should be considered.^ieng

Müllerian anomalies: a proposed classification. (An analysis of 144 cases).

Hospital and clinic charts for 100 patients with diagnosed Müllerian anomalies were reviewed. Reproductive history, type of therapy, and treatment results for those patients and for another 44 with a history of exposure to diethylstilbestrol and abnormal hysterosalpingographic findings were recorded and evaluated. The anomaly most frequently associated with reproductive failure was the septate uterus. A new classification, based on degree of failure of normal development, was used in separating the anomalies into groups with similar clinical manifestations, treatment, and prognosis for fetal salvage.

Artificial insemination using donor semen: a review of 171 cases.

This report represents a summary of our experience with 171 unselected cases of artificial insemination by donor (AID) over a 4-year period. It must be stressed that the study was retrospective and subject to many of the problems of analyzing such data. However, the information gained may aid the clinician in his approach to candidates for AID. The most critical points revealed by the survey are as follows: 1. Age, length of infertility, and proven fertility, within certain limitations, appear not to be of prime importance in determining the outcome of AID. 2. Of those patients conceiving, the majority will do so within three cycles of exposure, and 90% will have done so within six cycles of exposure. 3. An adequate trial of AID therapy should last at least 6 months. 4. Although the frequently reported conception rate of up to 70% may be expected in patients with correctable anovulation or with normal reproductive organs, a marked diminution in the success rate should be expected in candidates with disorders such as endometriosis, tubal disease, pelvic adhesions, and uterine abnormalities.

Post-ovarian wedge resection adhesive disease.

Our purpose was to determine how frequently adhesions develop after wedge resection for polycystic ovarian disease and to investigate the possibility of their contributing to subsequent infertility. Medical records spanning 15 years were compiled on 173 patients who had been followed for at least 1 year after ovarian wedge resection. Ovarian adhesions were found either by endoscopy or laparotomy at varying times after surgery in 59 of 111 patients not lost to follow-up. Forty-three patients who desired conception did not conceive; forty developed postoperative adhesions. Drug therapy for polycystic ovarian disease seems to offer results comparable to those of surgery and eliminates the risk of adhesions.

Uterine leiomyomata: etiology, symptomatology, and management.

PIP: 1 out of 4-5 women develop uterine leiomyomata, the most common solid pelvic tumors in women. This paper assesses the reports of 4714 myomectomies and records of 59 personal cases. Townsend et al. suggested that leiomyomata are unicellular in origin. Estrogen, growth hormone, and progesterone may influence the growth of the tumors. In the performance of myomectomy, the 2 major technical concerns are the minimization of blood loss and the prevention of postoperative adhesions. Although most leiomyomata are asymptomatic and grow slowly, 20-50% of the tumors are estimated to produce symptoms, the severity of which depends upon the number, size, and location of the tumors. The symptoms include menorrhagia, infertility, fetal wastage, pelvic pain/pressure, polycythemia, ascites, impingement, and related complications (e.g., ulceration and infection, fever, pain, uterine inversion, sarcomatous change). Asymptomatic patients with uteri of less than 10-12 weeks' gestational size require no more than observation at 6-month intervals regardless of fertility status. For women with uteri of 10-12 weeks gestational size or longer, management will depend on the patient's desire for fertility. Women desirous of fertility should have a 6-12 month trial for conception. If tumor growth is rapid, myometomy may be performed earlier. Women not desirous of fertility (e.g., pre- and post-menopausal) should have total abdominal hysterectomy and bilateral salpingo-oophorectomy. For symptomatic patients desirous of fertility, myomectomy using the transabdominal approach or hysteroscopy should be performed. For symptomatic patients not desiring fertility, dilatation and curettage and hysterectomy should be performed. With regard to oral contraceptive use, no studies have yet demonstrated that women on oral pills are at increased risk for growth of these tumors. Low-dose contraceptives should not be contraindicated in patients with leiomyomata if they desire to use this form of contraceptive. With IUD users, the device should be discontinued if bleeding occurs.^ieng

Treatment of endometriosis with danazol: report of a 6-year prospective study.

Presented are the results of a 6-year prospective study designed to evaluate the effectiveness of danazol for the treatment of endometriosis. Ninety-six patients completed 6 months of therapy at a dosage of 800 mg daily, and 107 patients completed therapy with 400 mg daily. No difference was reported in the incidence of side effects, regardless of dosage. Gross resolution of disease (as determined by second-look laparotomy or laparoscopy) was evaluated in 110 patients and found to be similar, regardless of dosage. Ovarian endometriosis greater than 1 cm was observed to respond significantly less well to danazol than peritoneal or ovarian disease less than 1 cm. Pregnancy rates for 157 patients with no other discernible causes of infertility were slightly higher for the 800-mg danazol regimen than for the 400-mg regimen. In patients with mild disease, the use of danazol alone resulted in pregnancy rates lower than those achieved with conservative surgery alone. Its use preoperatively for all stages of disease resulted in slightly higher pregnancy rates than when conservative surgery alone was employed. Danazol was less effective when used postoperatively. No differences were observed between three classification schemes in their ability to predict subsequent prognosis for conception.

Interim report a study of danazol for the treatment of endometriosis.

Ninety-six infertile women with laparoscopically confirmed endometriosis received danazol (800 mg daily) for 6 months. Despite their prevalence, side effects generally were tolerable and did not contraindicate use of the drug. The mean resolution of peritoneal endometriosis, measured in 44 patients, was 63%. However, individual responses varied considerably. The mean resolution of ovarian endometriosis in 28 patients was 45%. Resolution of less than 1 cm involvement (57%) was similar to that of peritoneal endometriosis, but for more extensive ovarian disease it was only 37% to 40%. Preoperative use of danazol facilitated surgical removal of disease and probably reduced the risk of postoperative adhesions. Pregnancy rates, though reported, are not analyzed because of the brevity of follow-up to date.

Saliva as a matrix for measuring free androgens: comparison with serum androgens in polycystic ovarian disease.

We report a simple and direct procedure for the measurement of circulating free testosterone concentrations by using saliva as a matrix rather than serum. There is a close correlation between saliva testosterone values measured by radioimmunoassay, calculated values of free testosterone, and free testosterone estimated by equilibrium dialysis. Our method is direct and has the advantage that the biologic fluid can be obtained routinely by noninvasive techniques outside the clinic during a course of therapy. We also show that a single saliva value is of greater diagnostic use than any of the currently used androgen assays. Testosterone was found to be elevated in the saliva of 17 infertility patients diagnosed as having polycystic ovarian syndrome, 14 of these patients were hirsute.

Linear regression analysis of ultrasound follicular growth series: evidence for an abnormality of follicular growth in endometriosis patients.

Follicular diameter growth is a highly linear function of time. Recently, the potential utility of linear regression-derived parameters for describing and comparing cycles of follicular growth was described. The linearity of growth, growth rate constant (K), calculated date of growth onset (Do), total growth period (TGP), menstrual age at apparent ovulation (MAov), and peak follicular diameter (PFD) have been calculated from the follicular growth series of a group of patients with laparoscopically diagnosed endometriosis (n = 46). These parameters were compared with those of a group of normal volunteers (n = 18). The authors found significant differences between endometriosis patients and controls in follicular growth rate and total growth period. The effect of patients' clomiphene citrate usage on growth parameters in these patients was examined. Abnormalities in interrelationships between the growth parameters were detected, suggesting the possibility of subtle defects in the regulation of follicular growth in these patients.

Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model.

To evaluate the potential benefit of recombinant tissue plasminogen activator (rt-PA) as an agent for reducing postoperative adhesions, a rabbit uterine horn model was studied. Fifty-five rabbits underwent laparotomy, at which time the uterus was abraded with scalpel and a thermal injury was induced with electrocautery. Before abdominal closure, rt-PA was applied topically in various dosages. Adhesions were evaluated at a second laparotomy performed 2 weeks later. Treatment significantly reduced both adhesion quantity (P less than 0.001) and adhesion density (P less than 0.001). In the second phase of the study, the efficacy of rt-PA as an adjunct to surgical adhesiolysis was investigated. Again, a dose-related treatment effect was observed (P less than 0.001). No wound healing or bleeding complications were seen.

Artificial insemination using homologous semen: a review of 158 cases.

One hundred fifty-eight women underwent artificial insemination with homologous semen (AIH) in an attempt to achieve conception. Only 15 (9.5%) were successful. Women with anatomical abnormalities were not excluded from the study and they were less successful than the normal women, but results were disappointing in both groups. The most frequently recorded indication for AIH was decreased density or motility of the husband's sperm, but pregnancy occurred in only 2 of the 48 cases in which sperm count was consistently less than 50 X 10(6)/ml and in only 3 of the 63 cases in which sperm motility was consistently less than 60%. When several semen analyses revealed considerable fluctuation in semen quality, the chances for impregnation by natural means appeared to be greater than the likelihood of success with AIH. The procedure does not seem to compensate for diminished count or motility, does not seem to be of particular value in cases of unexplained infertility, and appears to be indicated only in very special cases, if at all.

The use of synthetic luteinizing hormone-releasing hormone in induction of ovulation.

Each of 14 anovulatory patients received a single injection of 150 micrograms of synthetic luteinizing hormone-releasing hormone (LH-RH) in one induced menstrual cycle. In two subsequent cycles, patients were pretreated with clomiphene before LH-RH injection. Four patients received LH-RH after pretreatment with human menopausal gonadotropin (HMG) in another cycle. In each cycle, gonadotropin release and ovulation were recorded. All patients had previously failed to ovulate when treated with large doses of clomiphene. No patient ovulated following injection of LH-RH alone, although five patients exhibited a good pituitary response. Nine patients ovulated when they received LH-RH after pretreatment with clomiphene, and one patient ovulated when pretreated with HMG. The diagnostic value of a single injection of LH-RH is not clear. In the present study, gonadotropin response to LH-RH was not an entirely accurate predictor of a patient's ovulatory response in any of the four cycles. On the other hand, when clomiphene-LH-RH was administered, a good response was associated with ovulation in that cycle. The exact role of LH-RH in inducing ovulation is unclear, but the results of using LH-RH in conjunction with clomiphene are encouraging enough to warrant continued use and further study.

Peritoneal fluid plasminogen activator activity in endometriosis and pelvic adhesive disease.

Plasminogen activator activity in PF was assayed by the fibrinolysis method described by Strickland and Beers. In 45 patients studied, there were no discernible differences according to whether patients had endometriosis and/or pelvic adhesive disease. No differences were detected according to when in the menstrual cycle the sample of PF was obtained. These data are in concordance with a previous report and taken together suggest that there is no difference in fibrinolytic mechanisms in PF in patients with or without endometriosis and/or pelvic adhesive disease, when compared with control subjects. If such differences exist, they may be present in the tissues, per se, but are not discernible in PF.

Prolactin receptors in the ovary.

The binding of prolactin (PRL) to the plasma membranes of bovine and human ovaries was investigated using both homologous and heterologous 125I-prolactin. Saturation and Scatchard analysis demonstrated that human prolactin binds to human ovarian membranes with a Kd of 2 x 10(-10) M; to bovine ovarian membranes with a Kd of 1.9 x 10(-10) M; and to bovine corpora lutea membranes with a Kd of 1.9 x 10(-10) M. The concentrations of binding sites in bovine and human ovaries were 2.9 x 10(-15) moles/mg of protein and 2.0 x 10(-15) moles/mg of protein, respectively. The number of bindings sites in the bovine corpora lutea was 1.5 x 15(-15) moles/mg of protein. Specificity studies with bovine PRL, ovine PRL, human luteinizing hormone, human follicle-stimulating hormone, and bovine growth hormone showed this binding to be specific. Comparison of binding of PRL to membranes of other target and nontarget tissues suggests that the ovary is one of the primary target tissues. These data suggest that prolactin plays a role in the ovarian cycle.

Surgical correction of the septate uterus.

PIP: Metroplasty for septate uterus performed in 28 patients at Methodist Hospital in Houston is discussed. The preoperative fetal survival rate was 19.5%. Prior to laparotomy, D and C was performed in all patients. During the operation a lower abdominal transverse incision was used for abdominal exploration. The uterus was first divided from above downward in an anteroposterior direction until the endometrial cavity was entered. The incision was kept in the midline to minimize blood loss. Once the endometrial cavity was exposed, scissors were used to cut the septum bilaterally without excising it. Care was taken not to cut into the myometrium superiorly. The uterine walls were then reapproximated by simple interrupted no. 1 chromic catgut sutures that transversed serosa, myometrium, and endometrium. The first sutures were placed on the anterior and posterior aspects of the uterus just below the incision in the uterine wall. The remaining sutures were placed about .5 to 1 cm apart; none were tied until all sutures were in place. Closure was in a longitudinal anteroposterior direction along the same line as the incision. Approximation of the serosal surface was further enhanced by a running inverting 3-0 chromic catgut suture. In 16 patients, an IUD was placed in the uterine cavity before closure and left in place for 1 to 3 months. The frequency of associated endometriosis was 32.1%. Of the patients wishing to conceive, 73% became pregnant. The postoperative fetal survival rate was 87.5%. Delivery was by cesarean section.^ieng

Serum and peritoneal fluid proteins in women with and without endometriosis.

We examined the proteins in serum and peritoneal fluid of women with endometriosis (and of healthy controls) for evidence of an autoimmune response that might account for their impaired fertility. No antibodies against endometrial glycoproteins or against "progestin dependent endometrial protein" (PEP) were found in any serum or peritoneal fluid sample. Levels of PEP were not different in serum from women with moderate to severe endometriosis (n = 6), with mild endometriosis (n = 21), or from disease-free cycling controls (n = 19). PEP levels in peritoneal fluid from mild endometriosis and from controls did not differ but were elevated ten times in fluid obtained in the secretory phase from women with moderate to severe disease. This suggests that PEP levels in peritoneal fluid reflect the extent of ectopic endometrial growth. The salient finding was a heretofore undescribed protein (mol wt 70,000) in secretory phase peritoneal fluid samples (18/20) and its absence during the proliferative phase (0/35).