Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women.

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.

Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women.

OBJECTIVE: To compare reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility to outcomes in infertile couples with normal hysteroscopic findings. METHODS: Women with diagnoses of infertility who had hysteroscopic evaluations by a single surgeon between 1975 and 1996 were sent a routine follow-up questionnaire regarding their reproductive histories. All 92 subjects who were located responded to the questionnaire, and 78 met inclusion criteria: age under 45 years, at least 12 months of infertility, and at least 18 months of follow-up with attempts to conceive, including in vitro fertilization in women with bilateral tubal occlusion. RESULTS: Of the 78 subjects, 36 had myomectomies, 23 had polypectomies, and 19 had normal cavities. Among the three groups, there were no significant differences in age, type of infertility, length of infertility, or follow-up after the procedure. Polypectomy subjects had significantly higher pregnancy and live birth rates than women with normal cavities. Women who had myomectomies larger than 2 cm had significantly higher pregnancy and live birth rates, achieving statistical significance at a myoma size of 3 cm or greater for live births. Spontaneous abortion rates among first pregnancies after myomectomy, polypectomy, or normal study were similar: 31.5%, 27.7%, and 37.5%, respectively. CONCLUSION: Both hysteroscopic polypectomy and hysteroscopic myomectomy appeared to enhance fertility compared with infertile women with normal cavities. Despite concern that hysteroscopic resection of a large myoma might ablate a large surface area of the endometrial cavity, the reproductive benefit appears greater than the risk.

Utilizing routine sonohysterography to detect intrauterine pathology before initiating hormone replacement therapy.

OBJECTIVE: To assess the utility of performing routine sonohysterography in conjunction with endometrial thickness measurement for detecting intrauterine pathology in asymptomatic postmenopausal women. DESIGN: Asymptomatic postmenopausal women (n = 60, mean age 52.7 +/- 4.5 years, amenorrhea > or = 6 months, follicle stimulating hormone > or = 40 mIU/mL) were evaluated with sonohysterography followed by endometrial biopsy before initiating hormone replacement therapy. RESULTS: Hyperplasia was detected in 5 of 22 (22.7%) patients with endometrial thickness of > 5 mm and in 0 of 38 (0.0%) patients with endometrial thickness of < or = 5 mm. When sonohysterography was performed, intracavitary pathology was discovered in 14 of 38 (36.8%) patients with endometrial thickness of < or = 5 mm (10 polyps, three submucosal myomas, and one septate uterus) and 14 of 22 (63.6%) patients with endometrial thickness of > 5 mm (nine polyps, four submucosal myomas, and one Asherman's syndrome). CONCLUSIONS: Endometrial thickness of < or = 5 mm excludes hyperplasia but does not eliminate other intrauterine pathology that may be discovered by sonohysterography.

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Sonohysterographic screening before in vitro fertilization.

OBJECTIVE: To evaluate the use of sonohysterography for uterine screening before IVF. DESIGN: Prospective screening with sonohysterography and comparison with available hysterosalpingographic and hysteroscopic evaluations. SETTING: Private practice. PATIENT(S): Seventy-two women undergoing IVF-ET using their own or donor eggs. INTERVENTION(S): Sonohysterography was performed by instilling saline into the uterine cavity through an intracervical balloon catheter; there was concurrent vaginal sonographic visualization in all cases. MAIN OUTCOME MEASURE(S): Sonohysterographic findings and pregnancy rates. RESULT(S): Cavitary lesions were detected in 8 (11.1%) of 72 sonohysterographic examinations. Six of 8 cases were confirmed and treated by hysteroscopy. After sonohysterographic evaluation, 35 (48.6%) of 72 patients conceived, resulting in 25 ongoing or delivered pregnancies, 5 chemical pregnancies, and 5 spontaneous abortions. No statistically significant difference was observed in the pregnancy outcome for patients undergoing IVF who had sonohysterography compared with that for patients undergoing IVF during the same period who previously had a uterine evaluation by a different method. The estimated cost savings per patient undergoing sonohysterography instead of in-office hysteroscopy was $275. CONCLUSION(S): Sonohysterography offers advantages over in-office hysteroscopy and hysterosalpingography for evaluation of the uterus before IVF.

Pregnancy rates following hysteroscopic polypectomy, myomectomy, and a normal cavity in infertile patients.

Objective: To assess the reproductive benefits of hysteroscopic myomectomy and polypectomy for infertility when compared to infertile couples with a normal cavity at hysteroscopy.Material and Methods: All patients with a diagnosis of infertility who underwent hysteroscopic evaluation by a single surgeon between 1975 and 1996 were sent a questionnaire as routine follow-up regarding their reproductive history. All 100 subjects who were located responded to the questionnaire, and 78 subjects met the inclusion criteria; age <45 years, 12 months of infertility, and 18 months of follow-up with attempts to conceive including in vitro fertilization in patients with bilateral tubal occlusion.Results: Of the 78 subjects, 36 had undergone a myomectomy, 23 a polypectomy, and 19 had a normal cavity. Among the three groups there was no significant difference in their ages, types of infertility, length of infertility, or follow-up after the procedure. Using the Cox proportional hazard model, and adjusting for age, polypectomy patients had a significantly higher pregnancy rate (RR 3.89, P <.01) and a higher live birth rate (RR 2.42, P =.06) than patients with a normal cavity. Patients who had undergone a myomectomy also had a higher pregnancy rate (RR 2.02, P =.11) and live birth rate, but this did not achieve statistical significance. Pregnancy following a hysteroscopic myomectomy was associated with a larger fibroid resection (3.15 cm vs 2.5 cm P =.05). The spontaneous abortion rate following the myomectomy, polypectomy, or a normal study was equivalent, 28.1%, 23.1%, and 29.2%, respectively.Conclusions: Both hysteroscopic polypectomy and hysteroscopic myomectomy appear to enhance fertility when compared to infertile patients with a normal cavity. Despite concern that hysteroscopic resection of a large myoma may ablate a large surface area of the endometrial cavity, patients with larger myomas were more likely to conceive following resection.

Sonohysterography for screening in recurrent pregnancy loss.

OBJECTIVE: To evaluate the role of sonohysterography for screening of the uterine cavity in patients with recurrent pregnancy loss. DESIGN: Prospective evaluation of sonohysterography, including comparison with available hysterosalpingography and hysteroscopy. SETTING: University referral center. PATIENT(S): Thirty-four reproductive-aged women with at least two consecutive pregnancy losses. INTERVENTION(S): Sonohysterography was performed on all patients, using saline instilled through an endocervically placed balloon catheter with concurrent vaginal sonography. RESULT(S): Seventeen of 34 sonohysterograms (50.0%) demonstrated intrauterine abnormalities. Eighteen of 34 cases have undergone hysteroscopy or, in 1 case, laparoscopy. All confirmed the positive or negative sonohysterographic finding, resulting in a sensitivity and specificity of 100%. Additionally, 100% (12/12) of the defects were diagnosed accurately at sonohysterography when confirmed by surgery. Twenty-seven of 34 patients also had a hysterosalpingogram that demonstrated a 90.0% sensitivity and 20.0% specificity based on hysteroscopic findings, yet only 5 of 11 (45.5%) defects were diagnosed accurately at hysterosalpingography when compared with surgery. CONCLUSION(S): Sonohysterography is a highly sensitive, specific, and accurate screening tool for the evaluation of uterine cavitary defects associated with recurrent pregnancy loss and offers several advantages over hysterosalpingography.

Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in the human fallopian tube.

OBJECTIVE: The fallopian tube is the site of fertilization and early embryonic growth and a common site of ectopic implantation. Although the factors responsible for early embryogenesis and implantation are incompletely understood, leukemia inhibitory factor may have an important role in early embryonic development and implantation. We set out to evaluate the production and modulation of leukemia inhibitory factor in the fallopian tube. STUDY DESIGN: We first investigated leukemia inhibitory factor messenger ribonucleic acid levels in fallopian tubes. We then investigated leukemia inhibitory factor messenger ribonucleic acid and protein production in tubal epithelial and stromal cell cultures. RESULTS: Leukemia inhibitory factor messenger ribonucleic acid is expressed in the fallopian tube with only slight variation during the menstrual cycle; however, it is markedly elevated in association with ectopic pregnancy. The level is higher in the tubal mucosa than in the remaining layers and is higher in the more distal segments of the fallopian tube. Estradiol and progesterone did not modulate leukemia inhibitory factor expression in epithelial or stromal cell cultures. Interleukin-1 alpha, tumor necrosis factor-alpha, and transforming growth factor-beta enhanced leukemia inhibitory factor expression in epithelial and stromal cells, with transforming growth factor-beta 1 enhancing expression by fourfold in stromal cells. Epithelial cells secreted high levels of leukemia inhibitory factor compared with stromal cells (332 +/- 89 vs 25 +/- 42 pg/mg total protein). Yet stromal cells treated with transforming growth factor-beta alone or in combination with epidermal growth factor and platelet-derived growth factor, as well as TNF-alpha alone or in combination with interleukin-1 alpha enhanced secretion of leukemia inhibitory factor at or above the levels found with epithelial cells. CONCLUSIONS: We speculate that the high constitutive levels of leukemia inhibitory factor expressed in the ampullary portion of the fallopian tube may play a role in early embryonic development. Additionally, elevated expression with ectopic implantation and the marked induction of secretion in the tubal stroma by growth factors and cytokines suggest a link between inflammation, leukemia inhibitory factor, and tubal ectopic pregnancies.

Evaluation and management of chronic pelvic pain.

Evaluating patients with chronic pelvic pain is complex. A detailed medical history should be ideally supplemented by psychologic evaluation and assessment of the woman's social background. At the time of physical examination, the location and intensity of the pain should be mapped. Assessment of pain relief with the administration of a local anesthetic to trigger points or selected nerves may be useful in predicting the potential efficacy of surgical interventions such as uterosacral nerve ablation. Appropriate tests include pelvic ultrasound and magnetic resonance imaging. Ultimately, laparoscopy may provide the final diagnosis. Management should address the underlying cause(s) of pain; when this cannot be done, it should focus on treating the pain itself. When appropriate, empiric administration of antidepressants may be considered. In selected women, therapeutic goals may be achieved by electrical stimulation of nerves.

Large bowel-to-pelvic sidewall adhesions associated with chronic pelvic pain.

STUDY OBJECTIVES: To assess retrospectively the prevalence of colon-to-pelvic sidewall adhesions associated with pelvic pain or pelvic endometriosis, and to evaluate prospectively their prevalence compared with controls. DESIGN: A retrospective review of all patients undergoing laparoscopy for chronic pelvic pain between August 1992 and September 1993; and abased on a power analysis, a prospective comparison of women undergoing laparoscopy for chronic pelvic pain with those undergoing laparoscopy for tubal sterilization between October 1994 and December 1995. SETTING: A university-associated teaching hospital. PATIENTS: Fifty women in the retrospective portion, and 30 women (15 in each group) in the prospective portion. MEASUREMENTS AND MAIN RESULTS: Of the 50 women undergoing laparoscopy for pelvic pain, 47 (94%) had either right- or left-sided colon-to-sidewall adhesions, and these adhesions were more common than any other type of intraabdominal adhesion, 94% versus 58%. Thirty-eight (76%) of these women had visual and 25 (50%) histologic evidence of endometriosis. The prospective study revealed that women with pelvic pain had a higher rate of colon-to-sidewall adhesions than controls (93.3% vs 13.3%) and a correspondingly higher rate of visualized endometriosis (73.3% vs 6. 7%). Right-sided paracolic adhesions were both more common than left-sided adhesions (87.7% vs. 46.7%) and were more often extensive than minimal (46.7% vs 6.7%). CONCLUSIONS: Colon-to-sidewall adhesions occur in the majority of patients with chronic pain, whereas they are an uncommon finding in the general population. The lateral gutters are dependent regions of the abdominal cavity that are susceptible to the spread of peritoneal endometriosis or other inflammatory processes, and should be evaluated at diagnostic laparoscopy for chronic pelvic pain.

Circulating Fc gamma receptor-specific autoantibodies in localized and systemic scleroderma.

BACKGROUND: Anti-Fc gamma receptor (anti-Fc gamma R) autoantibodies occur in patients with systemic scleroderma. Their clinical significance is unknown. OBJECTIVE: Our purpose was to determine the incidence of anti-Fc gamma R autoantibodies in patients with localized and systemic scleroderma and to examine the relation between these autoantibodies, the severity of the disease, and the presence of other autoantibodies. METHODS: Patients were placed into three clinical groups: three had diffuse systemic scleroderma, 47 had limited systemic scleroderma, and nine had localized systemic scleroderma. Antinuclear antibody titer and pattern were measured by indirect immunofluorescence with human epithelial (HEp)-2 cells and tissue sections, whereas anti-Scl-70 antibodies were measured by gel diffusion technique. Anti-Fc gamma R autoantibodies were measured in serum from patients and from 25 healthy persons by enzyme-linked immunosorbent assay with human recombinant Fc gamma RII (CD32) and Fc gamma RIII (CD16). RESULTS: Anti-Fc gamma R autoantibodies were detected in 54% of patients and in none of the healthy control subjects. Autoantibodies were present in all three clinical groups and were most frequently directed against Fc gamma RIII. Correlation between patients' clinical and laboratory data and anti-Fc gamma R autoantibodies could not be demonstrated. CONCLUSION: The presence of anti-Fc gamma R autoantibodies in the serum of patients with either systemic or localized scleroderma and the lack of these autoantibodies in healthy persons suggest that they may play a role in the pathogenesis of these diseases.

Endosalpingiosis found at laparoscopy for chronic pelvic pain.

OBJECTIVE: To assess a correlation between endosalpingiosis and pelvic pain. DESIGN: A retrospective analysis of every patient undergoing laparoscopy for chronic pelvic pain at Yale-New Haven Hospital by one surgeon from August 1992 through October 1993 was performed, focusing on those cases with endosalpingiosis. RESULTS: Of 51 laparoscopies performed for chronic pelvic pain, 37 demonstrated visual evidence of implants and pathology specimens were read as either endometriosis or endosalpingiosis in 23 cases. Of those 23 cases, 6 demonstrated endosalpingiosis, and 4 of those 6 demonstrated both endosalpingiosis and endometriosis. In all six cases endosalpingiosis was found in locations consistent with the patients' pelvic pain symptoms, and all six patients experienced relief from their pain symptoms after surgery. CONCLUSIONS: Endosalpingiosis may be found in association with chronic pelvic pain. The pelvic distribution of endosalpingiosis in patients with chronic pain is consistent with that generally found in endometriosis.

Baseline cyst formation after luteal phase gonadotropin-releasing hormone agonist administration is linked to poor in vitro fertilization outcome.

OBJECTIVE: To investigate the prognostic significance of baseline ovarian cysts after luteal phase GnRH agonist (GnRH-a) administration for IVF-ET. DESIGN: All nondonor IVF-ET cycles in one program in which luteal phase GnRH-a was administered between July 1993 and January 1994 were assessed for the formation of baseline ovarian cysts defined as a mean diameter > or = 15 mm. Outcome data from the IVF cycles were compared between patients with and without baseline ovarian cysts. RESULTS: Of 78 IVF cycles, baseline cysts > or = 15 mm were noted in 26 cycles. Cycles in which cysts were formed were associated with significantly older patients with significantly higher baseline FSH values. Cycles in which cysts were present demonstrated fewer follicles, retrieved oocytes, and embryos. Cyst cycles also demonstrated a lower peak E2 level, implantation rate, and clinical pregnancy rate (PR) per initiated cycle (7.7% versus 32.7%). Cyst cycles also demonstrated a higher cancellation rate. Logistic regression modeling, accounting for age, confirmed significantly lower clinical PRs in cycles with a baseline cyst. CONCLUSIONS: Baseline cyst formation after luteal phase GnRH-a administration is both a marker for poor responders and a reliable predictor of poor stimulation and low PRs in a given IVF-ET cycle.

Infantile (desmoid-type) fibromatosis.

Infantile (desmoid-type) fibromatosis is an uncommon, locally aggressive tumor that is seldom reported in the dermatologic literature. We describe a case of infantile (desmoid-type) fibromatosis in a 2-year-old girl. Surgical disposition entailed amputation of the affected digit. Our report is intended to heighten awareness of this potentially fatal tumor, and emphasize the importance of timely diagnosis and treatment.

Ovulation triggering in clomiphene citrate-stimulated cycles: human chorionic gonadotropin versus a gonadotropin releasing hormone agonist.

PURPOSE: To compare the use of human chorionic gonadotropin (hCG) to a gonadotropin releasing hormone (GnRH) agonist, nafarelin, in initiating ovulation and supporting the luteal phase after priming with clomiphene. METHODS: In 26 infertile women 50 mg clomiphene citrate produced a preovulatory-size follicle. Then, 11 women were randomized to receive two 400-micrograms doses of nafarelin intranasally 16 h apart, and 15 women were injected intramuscularly with 5000 IU of hCG (luteal day 0 = LD0). Starting on LD6, 7 more 400-micrograms doses of nafarelin were repeated on an every 16-h schedule or a single 2500 IU dose of hCG was given, respectively. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), and hCG were measured. On LD13, endometrium was evaluated with ultrasonography and biopsy in 19 nonpregnant women. RESULTS: As judged by a threefold rise in serum LH, an LH surge was detected on LD1 in all 11 nafarelin patients, but in only 8 hCG patients (P = 0.01). LH and FSH levels were significantly higher on LD1, 7, and 8 and were significantly suppressed on LD13 in the nafarelin group. All patients had mid-luteal P levels greater than 10 ng/ml and luteal phases longer than 13 days. Significantly different luteal E2 or P levels were noted only on LD13, with lower values in the nafarelin group. Pregnancies were achieved in 3 of 11 nafarelin cycles and 2 of 15 hCG cycles. Luteal phase defects were also similar: 4 of 8 nafarelin patients and 7 of 11 hCG patients. CONCLUSION: Nafarelin or hCG in conjunction with clomiphene can result in viable pregnancies, but is associated with low pregnancy rates and a high incidence of luteal phase defects.

Dilutional hyponatremia during hysteroscopic myomectomy with sorbitol-mannitol distention medium.

To determine the frequency of hyponatremic complications during hysteroscopic myoma resections using sorbitol-mannitol distending medium and its relationship to operative time, fluid balance, and myoma size, we reviewed all operative hysteroscopic procedures performed by the Section of Reproductive Endocrinology and Fertility at Yale-New Haven Hospital over a 1-year period during which that medium was used. Twenty-six cases were identified of which seven involved hysteroscopic myoma resections. Hyponatremia occurred in four of the seven patients, and in one it was associated with severe posttransurethral prostatic resection (post-TURP) syndrome. The degree of hyponatremia varied roughly in direct proportion to fibroid volume and fibroid volume as a percentage of uterine volume. No relationship was found between the degree of hyponatremia and operating time, estimated submucosal volume, and uterine volume. We conclude that dilutional hyponatremia and the post-TURP syndrome may occur with the use of sorbitol-mannitol distension medium during hysteroscopy. They occur more frequently during operative hysteroscopy to resect myomata, with myoma size and myoma volume expressed as a percentage of uterine volume possibly influencing the degree of hyponatremia.

Duplicate cervix and vagina associated with infertility, endometriosis, and chronic pelvic pain.

BACKGROUND: Müllerian anomalies are associated with several gynecologic complications including endometriosis, infertility, and pelvic pain. CASE: A woman with duplicate cervix and a non-communicating longitudinal vaginal septum, but no other uterine anomalies, presented with pelvic pain, secondary infertility, and a long history of endometriosis. She was treated with operative laparoscopy and excision of the vaginal septum. CONCLUSION: A thorough evaluation, including history, physical examination, and appropriate imaging techniques (hysterosalpingography and magnetic resonance imaging) facilitates accurate diagnosis of anatomical defects and any associated disease in cases of unusual müllerian anomalies. An accurate preoperative diagnosis allows a planned, efficient surgical approach.

Peristomal pyoderma gangrenosum.

A patient with Crohn's disease and peristomal pyoderma gangrenosum is described. This patient is unique because she had a rapid response to intralesionally injected steroids. This treatment is ideal for peristomal pyoderma gangrenosum because it is administered intermittently when the ostomy appliance is changed and it does not interfere with adhesion of the device. All 11 cases of peristomal pyoderma gangrenosum described in the literature are reviewed.