Elevated serum Chlamydia trachomatis IgG antibodies. What do they mean for IVF pregnancy rates and loss?

OBJECTIVE: To evaluate the impact of elevated serum Chlamydia IgG antibodies (Ab) on in vitro fertilization (IVF) outcome in a large infertility population. STUDY DESIGN: One hundred ninety-four women under 40 years of age undergoing a total of 316 IVF cycles were evaluated. All couples with positive serum Chlamydia IgG Ab were pretreated with doxycycline, 100 mg twice daily, for 10 days prior to the first IVF cycle. RESULTS: One hundred seven women (55.2%) had elevated serum Chlamydia IgG Ab. One hundred seventy-two IVF cycles (54.4%) were in patients with elevated Ab as compared to 144 cycles (45.6%) in controls with negative Ab. There were no significant differences in mean age, number of mature oocytes obtained or number of embryos transferred between the two groups. Patients with elevated IgG Ab had on ongoing pregnancy rate of 30.2% (52/172) and implantation rate of 13.5% (101/746) as compared to 34.7% (50/144) and 13.6% (88/649) in the negative Ab group, respectively (P = NS for both). Two ectopic pregnancies occurred in the elevated Ab group (1.2%, 2/172) vs. none in the negative Ab group. The incidence of early pregnancy loss was 8.7% (15/172) and 9.7% (14/144) in the positive and negative Ab groups, respectively (P = NS). CONCLUSION: The prevalence of elevated serum Chlamydia IgG Ab in patients presenting for IVF was higher than in the general population. In the absence of an active genital tract infection, the presence of elevated serum Chlamydia IgG Ab was not associated with a poor IVF outcome when couples were treated with antibiotics prior to stimulation. In addition, there was no correlation between IVF outcome and quantitative IgG Ab titers in women with elevated serum Chlamydia Ab. We recommend that all couples with elevated titers be treated with doxycycline prior to the first IVF attempt to optimize pregnancy rates and minimize infectious complications.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

OBJECTIVE: to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). STUDY DESIGN: Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. RESULTS: Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. CONCLUSION: The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.

Bromocriptine reverses the inhibitory effect of macrophages on human sperm motility.

OBJECTIVE: To determine the effects of PRL suppression on the activation of murine peritoneal macrophages and their subsequent effects on human sperm motility. DESIGN: Laboratory study. INTERVENTIONS: Mice were treated with subcutaneous implants of 2.5 mg bromocriptine pellets 7 days before bacillus of calmette and guerin (BCG), a strain of Mycobacterium bovis, injection for activation of macrophages. Bromocriptine treatment, which significantly suppressed circulating PRL levels, continued through the day of peritoneal macrophage collection. Macrophages were subsequently cultured for 4 days and culture supernatant was collected. MAIN OUTCOME MEASURES: Human sperm were incubated for 4 hours in the presence of culture medium or culture supernatant from control and treated mice. Motion analysis was performed at 0, 2, and 4 hours. RESULTS: A significant decrease in human sperm motility was observed in the presence of culture supernatant from activated murine peritoneal macrophages. After 4 hours of incubation, sperm motility decreased from 69% +/- 3% in the nonactivated macrophage control group to 37% +/- 6% in the BCG- activated macrophage group. The suppressive effect of soluble products of activated macrophages on human sperm motility was reversed when mice were rendered hypoprolactinemic with bromocriptine. Motility after 4 hours was 56% +/- 3% in the BCG-bromocriptine group. Simultaneous administration of bromocriptine and PRL (100 ng per mouse daily) restored the inhibitory effect of soluble products of activated macrophages on sperm motility (36% +/- 5% motile). CONCLUSIONS: PRL may modulate the deleterious effects of activated macrophages on human sperm motility, thereby suggesting novel and useful methods for the modification of the immune response in early reproduction.

Cervical pregnancy: case reports and a current literature review.

The increasing number of reports of successful conservative treatment of cervical pregnancy, such as using the folinic acid antagonist methotrexate, constitutes a breakthrough in the management of this unusual but potentially life-threatening complication of pregnancy. We are reporting two cases of cervical pregnancy, both diagnosed in the first trimester of pregnancy. The first one was successfully treated by transvaginal ultrasound-guided administration of 2 mEq KCI intraamniotically in order to stop the fetal heart activity, followed by administration of 84 mg of methotrexate intraaminiotically (1 mg/kg); whereas in the second case, we encountered a technical failure of the above method. Both patients expressed desire to maintain their reproductive capability. These two cases gave us the opportunity to review the recent literature on cervical pregnancy.

Colchicine and post-inflammatory adhesions in a rabbit model: a dose-response study.

OBJECTIVE: To determine the dose-response relationship of colchicine in reducing inflammatory adhesive disease secondary to Neisseria gonorrhoeae in the rabbit. METHODS: Following intrauterine inoculation of a suspension of N gonorrhoeae, the rabbits were divided into five groups of 11 rabbits each. The control group received no medications. The remaining four groups received 0.1, 0.5, 1, and 2 mg, respectively, of colchicine intramuscularly daily for 14 days. The day after the last injection of colchicine, the peritoneal cavity was explored and assessed for the presence, number, and grade of adhesions. RESULTS: With increasing doses of colchicine, the incidence of adhesions decreased. A linear model (log [dose + 0.5]) showed, however, that as the dose of colchicine increased, the response tended to plateau (P < .05). CONCLUSION: In this model, colchicine was effective in preventing inflammatory adhesions in the rabbit. Increasing doses produced a greater effect in reducing adhesion formation. However, there was a plateau of the response at the 1-mg dose.

Effects of colchicine on pelvic adhesions associated with the intrauterine inoculation of Neisseria gonorrhoeae in rabbits.

OBJECTIVE: To determine whether colchicine, an anti-inflammatory drug, is effective in reducing adhesion formation in a rabbit model in which pelvic inflammation was produced by injection of a suspension of Neisseria gonorrhoeae into the uterine horn. METHODS: Following inoculation, the rabbits were divided into four groups of 11 animals each. The control group received 1 mL saline intramuscularly (IM) for 14 days. Another group received one 100-mg dose of ceftriaxone IM 2-4 hours after inoculation. The third group received one 100-mg dose of ceftriaxone IM 2-4 hours after inoculation and 1 mg colchicine IM daily for 14 days. The fourth group received 1 mg colchicine IM daily for 14 days. The day after the last injection of colchicine, the rabbits were sacrificed and the abdominal cavities were explored to determine the number and grade of adhesions. RESULTS: The incidence of adhesions in the control group was similar to that in the antibiotic-treated group, suggesting that antibiotics do not prevent adhesions in this model. Similarly, the incidence of adhesions in the colchicine and antibiotic group was not different from that in the group receiving colchicine alone. However, the colchicine-treated groups had significantly fewer adhesions than the groups not treated with colchicine (P < .0005). CONCLUSIONS: In this model, antibiotics alone did not prevent the formation of adhesions. Colchicine, alone or in combination with antibiotics, was effective in preventing bacteria-induced pelvic adhesions. Therefore, colchicine may offer a novel approach to the prevention of adhesions associated with pelvic inflammatory disease in women.

The menstrual cycle: relations of biophysical and hormonal determinations in normal women of reproductive age.

Appropriate relationships between circulating levels of 17 beta-E2 and P are necessary for normal endometrial development and blastocyst implantation. The aim of this study was to relate biophysical and biochemical measurements obtained during the menstrual cycle of six healthy women in 25 menstrual cycles. One hundred eighteen vaginosonographic determinations of the endometrial thickness together with serum E2 and P assays were performed at 5-day intervals. The three parameters studied were standardized by the formula: observation minus mean determination for that parameter divided by the standard deviation of that parameter. Using this common unit, the physiological relations between ultrasonographically determined endometrial thickness, E2, and P were readily seen.

Nonsurgical treatment of a viable cervical pregnancy with intra-amniotic methotrexate.

Although a rare complication of gestation, the possibility of fertility loss is no more serious than with a cervical pregnancy. A case of a viable cervical pregnancy treated with ultrasound guided transabdominal aspiration and intra-amniotic methotrexate administration is presented. When the diagnosis is made early in gestation this method should be considered for the treatment of a cervical pregnancy when future fertility potential is desirable.

Successful treatment of a live cervical pregnancy with methotrexate and folinic acid. A case report.

A case of cervical pregnancy with a fetal pole, fetal cardiac activity and a serum beta-human chorionic gonadotropin level reaching a peak of 60,000 mIU/mL was treated successfully with methotrexate and folinic acid. These criteria have been considered a contraindication to conservative medical management. Serial beta-human chorionic gonadotropin levels and sonography were used to diagnose the pregnancy and monitor therapy. Complications were limited to transient conjunctivitis and blood loss anemia. The patient's fertility potential was preserved.

Evaluation of the human gonadotroph free alpha-subunit secretory pools by administration of gonadotropin hormone-releasing hormone into normal subjects at different phases of the ovarian cycle.

The specificity of a monoclonal antibody RIA for the measurement of free alpha-subunit in plasma is presently documented. This RIA was used to explore the pituitary gonadotroph free alpha-subunit reserve in normal ovulating women stimulated with gonadotropin hormone-releasing hormone (GnRH). RIA specificity was established by means of competitive inhibition curves with various glycoprotein hormone preparations, and Sephadex G-100 exclusion chromatography of purified hFSH (1-2), hLH (LER 960) and pituitary extract. The 3.8% and 5.5% crossreactivities of hFSH 1-2 and hLH LER 960 were shown by exclusion chromatography to result in part from free alpha-subunit contamination in these purified preparations. Pituitary extract chromatography indicated hFSH and hLH cross-reactivity below 2.5% and 1.5%, respectively. Normal females were stimulated with GnRH throughout the cycle: 3 tests were performed on Day 7, 1 test on Day 13, 16, 17 and 22, respectively, and 2 tests on Day 24. GnRH stimulation consisted of an initial 100 micrograms bolus (time 0) followed at 2 h by a 12.5 micrograms/h constant infusion, and a second 100 micrograms bolus at 5 h. In all subjects, baseline free alpha-subunit values were below 2 ng/ml. Total free alpha-subunit secretion was markedly enhanced in subjects Day 13 and 16, in concert with total hLH and hFSH secretion. In the three subjects Day 7, free alpha-subunit was released only after the second GnRH bolus. In periovulatory subjects, free alpha-subunit secretion became apparent after the initial bolus and with constant GnRH infusion. In the three subjects Day 22 and 24, peak levels of free alpha-subunit were obtained after the second GnRH bolus.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism.

A causal link between hypothyroidism and spontaneously occurring ovarian hyperstimulation syndrome is suggested by analysis of data from a patient with myxedema and review of data from animal research.

Carbamazepine-induced hyponatremia after transabdominal follicular ultrasound examination.

We report a serious complication after transabdominal follicular ultrasound monitoring in a patient taking CBZ for a chronic seizure disorder. She developed severe hyponatremia after a large volume of water intake for bladder filling before her scan. We recommend the use of transvaginal US scans in such patients or as an alternative to the transabdominal approach in all patients, since we have found good patient tolerance and excellent pelvic organ visualization without the need for bladder filling.

Pathological hyperprolactinemia suppresses hot flashes in menopausal women.

Hyperprolactinemia impairs pituitary-gonadal function in young women, but its effect in menopausal women is not known. The purpose of this report is to describe the effect of hyperprolactinemia on gonadotropin secretion and hot flashes in menopausal women before and after treatment with a dopamine agonist. We studied two such women with prolactinomas. Both had plasma LH and FSH levels in the range found in premenopausal women and no hot flashes. Treatment with bromocriptine was associated with normalization of plasma PRL levels, elevation of plasma gonadotropin levels, and the onset of menopausal hot flashes in both patients. We conclude that hyperprolactinemia can inhibit the augmented gonadotropin secretion that occurs in postmenopausal women and prevent hot flashes.

Life table analysis of intrauterine insemination pregnancy rates.

One hundred twenty-eight couples undergoing intrauterine inseminations were retrospectively reviewed. Life table methodology was used to analyze cumulative pregnancy rates and monthly fecundability. Respective 6- and 12-month cumulative pregnancy rates for each diagnostic group receiving intrauterine insemination were: cervical factor, 28.6% and 42.8%; male factor, 16.7% and 16.7%; female immune factor, 66.7% and 100.0%; male immune factor, 37.5% and 68.8%; and empiric treatment, 60.0% and 60.0%. There was no difference in pregnancy rates between sperm processed with a swim-up in Ham's F-10 or a two-gradient Percoll system. Abnormal sperm penetration assay results in patients with male factor did significantly (p = 0.05) lower the pregnancy rate. It is concluded that if no pregnancy has occurred after six cycles of inseminations, further workup or other treatment may be initiated, but additional pregnancies can be achieved from the seventh through the twelfth cycles of intrauterine insemination.

Antibody binding patterns in infertile males and females as detected by immunobead test, gel-agglutination test, and sperm immobilization test.

Sera from 214 infertile patients were assayed for antisperm antibodies using the IBT, GAT, and SIT. The new IBT methodology was compared with the more classical tests. Although SIT and GAT did not correlate to any particular antibody class, both were negative if IgA was present alone. The immunoglobulin class presented a preferential sperm region binding site: IgG to the head and tail, IgM to tail tip only, IgA to head and tail. Furthermore, these immunoglobulins from the serum of male patients bound differently to sperm than immunoglobulins from female serum. Finally, we were able to calculate the relative sensitivity, specificity, and predictive values for these tests.

The effect of peritoneal macrophage incubates on the spermatozoa assay.

PFM have been implicated as a possible cause of infertility in endometriosis. Previous work from our laboratory has indicated that medium incubated with PFM caused a significant decrease in sperm penetration when added to the sperm penetration assay (SPA). To further delineate this finding, medium incubated with killed macrophages, heat-inactivated medium, and various concentrations of macrophage media were added to the SPA. Analysis of the data implied that there is a 1.536% decrease in penetration for every 1% increase in the concentration of PFM medium. Heat-inactivated medium and medium incubated with dead PFM both produced penetrations statistically different from the control. We conclude that medium incubated with PFM is capable of decreasing sperm penetration as measured in the SPA in a dose-dependent fashion. Furthermore, the substance responsible for this decrease appears to be heat-stable and released from dead as well as live macrophages.

Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropins for ovarian stimulation in an in vitro fertilization program.

This report compares the effects of human menopausal gonadotropin (hMG) and purified urinary human follicle-stimulating hormone (hFSH) protocols in patients with irreparable tubal disease as the sole indication for in vitro fertilization-embryo transfer (IVF-ET). The hFSH protocol was associated with significantly more uniform folliculogenesis and more effective steroidogenesis than the one using hMG. In addition, the hFSH protocol showed a trend toward more oocytes per laparoscopy and more embryos per transfer than the hMG group, although the difference was not statistically significant. More oocytes in the hMG group were classified as immature when compared with the hFSH group (P less than 0.05). Pregnancy rates in both groups were not significantly different. An allergic drug reaction that occurred in one patient on the hFSH protocol is the first such reaction reported with hFSH in the literature. The hFSH protocol is associated with a trend toward parameters that correlate with improved success rates in the IVF-ET program.

Gonadotropins augment maturation and fertilization of human immature oocytes cultured in vitro.

The inclusion of hMG in the culture medium for immature human oocytes results in improved maturation and fertilization rates. The resulting increased number of conceptuses available for transfer may improve the incidence of IVF pregnancy.

Free alpha-subunit response to gonadotropin-releasing hormone in women with polycystic ovaries.

The response of glycoprotein hormone free alpha-subunit to gonadotropin-releasing hormone (GnRH) was evaluated in 12 women with polycystic ovaries (PCOs). Six of these women were premedicated for 3 days with micronized 17 beta-estradiol before receiving a 100-micrograms bolus of GnRH. In nonmedicated PCO patients, GnRH did not significantly alter basal free alpha-subunit levels. In four of the six PCO patients receiving estrogen premedication, a significant increase in free alpha-subunit was observed; these four patients had low progesterone levels at the time of the GnRH test. Among the six premedicated patients, two had elevated (greater than 4 ng/ml) progesterone levels, and the GnRH tests showed no significant effect on the levels of free alpha-subunit. The study revealed a dissociation between the free alpha-subunit responses to GnRH and the responses of luteinizing hormone; a closer relationship was observed between free alpha-subunit and follicle-stimulating hormone responses. It was concluded that the lack of a free alpha-subunit response to GnRH in PCO patients is not due to a primary inability of the pituitary gonadotroph to produce free alpha-subunit but is a consequence of an altered estrogenic milieu, and a free alpha-subunit response to GnRH may reflect the replenishment of both follicle-stimulating hormone and luteinizing hormone in the gonadotrope.