Uncommon presentations of an uncommon entity: OHVIRA syndrome with hematosalpinx and pyocolpos.

Müllerian malformations result from defective fusion of the Müllerian ducts during development of the female reproductive system. The least common form of these malformations is Herlyn-Werner-Wunderlich syndrome characterized by obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). The most common presentation of this syndrome is a mass secondary to hematocolpos, pain, and dysmenorrhea. Clinical diagnosis is very challenging and requires imaging studies in which ultrasound and MRI play an essential role in the diagnosis, classification and treatment plan. We report two cases of this syndrome, featuring two very rare clinical presentations: hematosalpinx and pyocolpos. The clinical course of the pathology is not standard and each patient is treated accordingly.

Intra-peritoneal leiomyoma of the round ligament in a patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.

BACKGROUND: The occurrence of an extra-uterine leiomyoma, arising from the intra-peritoneal portion of the round ligament in a lady with Müllerian agenesis diagnosed at the age of forty is extremely rare. We report a case of this rare combination in a Middle Eastern woman. CASE: A 40 years old lady, primarily amenorrheic, presented to our clinic for an infertility consultation. The work- up showed features suggestive of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a leiomyoma arising from the intra-peritoneal part of the round ligament.

Effect of weight gain during pregnancy on heart rate variability and hypotension during caesarean section under spinal anaesthesia.

The purpose of this study was to assess the effect of antenatal weight gain on baseline heart rate variability and incidence of hypotension in singleton parturients with a normal pre-pregnancy body mass index, presenting at term for elective caesarean section under spinal anaesthesia. Sixty-six parturients, of ASA physical status 1-2, were allocated to one of three groups according to their weight gain during pregnancy: < 11 kg; 11-16 kg; and > 16 kg. Mean (SD) approximate entropy of baseline heart rate was significantly higher in the < 11 kg group (0.27 (0.11)) compared with the 11-16 kg group (0.14 (0.08)) and the > 16 kg group (0.14 (0.07)) (both p < 0.001). The incidence of hypotension in the < 11 kg group (17/22; 77%) was significantly higher than in the 11-16 kg group (7/22; 32%) (p = 0.006) and the > 16 kg group (8/22; 36%) (p = 0.01). We conclude that weight gain < 11 kg during pregnancy is associated with increased baseline heart rate variability and a higher incidence of hypotension at the time of elective caesarean section under spinal anaesthesia.

Psammoma bodies in cervicovaginal smears.

OBJECTIVE: To estimate the prevalence of psammoma bodies in routine cervical cytology specimens and describe clinical diagnoses associated with them in pre- and postmenopausal women. METHODS: We identified all reports that contained psammoma bodies from a retrospective review of 34,816 cytology reports over 4 consecutive years from the computerized pathology database at Yale New-Haven Medical Center. Slides were reviewed to confirm and qualify psammoma bodies. Medical records of women with psammoma bodies were reviewed and information on follow-up was collected. RESULTS: We identified 18 women with psammoma bodies on their Papanicolaou smears. The median age was 49.5 years (range 17--78 years). Seven of eight postmenopausal women had gynecologic malignancies. Five presented with postmenopausal bleeding and had uterine serous or clear-cell carcinomas. One presented with a pelvic mass that was ovarian serous carcinoma. Another had a serous carcinoma of the fallopian tube with only psammoma bodies on Papanicolaou smears. Only one of the remaining 11 nonmalignant cases was a postmenopausal woman. CONCLUSION: The prevalence of psammoma bodies in consecutively screened Papanicolaou smears was 18 of 34,816. Psammoma bodies on Papanicolaou smears are ominous in postmenopausal women. Their presence in asymptomatic premenopausal women warrants further evaluation, but not necessarily surgical exploration.

Empty follicle syndrome: evidence for recurrence.

The empty follicle syndrome (EFS) is a frustrating condition in which no oocytes are retrieved in an IVF cycle. Although this is an infrequent event in IVF patients, the economic consequences as well as the emotional frustration of a cancelled cycle due to the inability to obtain oocytes are enormous. The mechanisms responsible for EFS remain obscure, though many hypotheses have been put forward ranging from dysfunctional folliculogenesis to a drug-related problem. We found that the EFS is a rare event (1.8% of oocyte retrievals) but with profound implications for counselling the couple about their future reproductive performance. The chances of recurrence of EFS increase with the age of the patient (24% recurrence rate for the 35-39 year age group, and 57% for those over 40 years). We postulate that ovarian ageing, through altered folliculogenesis, may be implicated in the aetiology of EFS and its recurrence.

Macrophage derived growth factors modulate Fas ligand expression in cultured endometrial stromal cells: a role in endometriosis.

Fas-Fas ligand (FasL) interactions play a significant role in the immune privilege status of certain cell populations, and several cytokines and growth factors can modulate their expression. When a FasL-expressing cell binds a Fas-bearing immune cell, it triggers its death by apoptosis. In this study, we demonstrate that normal human endometrial epithelial but not stromal cells express FasL. Moreover, we showed that macrophage-conditioned media induced FasL expression by endometrial stromal cells in a dose-dependent manner. To elucidate which macrophage product was responsible for the up-regulation of FasL, endometrial stromal cell cultures were treated with the macrophage products platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta1, and basic fibroblast growth factor (bFGF). The first two (which are known to be elevated in the peritoneal fluid of women with endometriosis) induced a dose-dependent up-regulation of FasL expression, which was specifically inhibited by the antibody. Interestingly, bFGF (which is not elevated in peritoneal fluid of women with endometriosis) did not induce any response. These results suggest that the pro-inflammatory nature of the peritoneal fluid of women with endometriosis induces the FasL expression by regurgitated endometrial cells, and signals Fas-mediated cell death of activated immune cells. This could be a mechanism for endometrial cells to escape immune surveillance, implant and grow.

Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles.

OBJECTIVE: To compare two methods of timing IUI, urinary LH monitoring and transvaginal ultrasonography/ hCG timing of ovulation, in patients receiving clomiphene citrate. DESIGN: Prospective, randomized, crossover study. SETTING: Yale University Reproductive Medicine Center. PATIENT(S): Infertile couples undergoing IUI because of unexplained infertility, anovulation, or male factor infertility. INTERVENTION(S): Patients received clomiphene citrate on days 3-7 of the menstrual cycle and were randomized initially to one of two monitoring protocols. In protocol A, urinary LH monitoring was used to time IUI. Urinary LH levels were determined daily with the use of commercial kits, starting on day 10 of the cycle. When urinary LH was detected, IUIs were performed daily for the next 2 days. In protocol B, ultrasound monitoring of folliculogenesis was performed until a leading follicle of > or = 18 mm was noted, at which time hCG (10,000 IU) was given intramuscularly and IUIs were performed daily for the next 2 days. If no pregnancy occurred, the couple crossed over to the alternate protocol for the next cycle and continued this alternating therapy for a total of four cycles. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle. RESULT(S): One hundred forty-one cycles were completed. In these cycles, six pregnancies occurred, for an overall pregnancy rate of 4.26% per cycle. The pregnancy rate with LH-timed IUI was 4.29% (3/70) and that with hCG-induced ovulation was 4.23% (3/71); the difference was not statistically significant. CONCLUSION(S): Timing IUI with the use of a relatively expensive and time-consuming method such as ultrasound monitoring of folliculogenesis and hCG induction of ovulation does not appear to produce an increased pregnancy rate over urinary LH monitoring of ovulation.

Identification and characterization of an ascorbic acid transporter in human granulosa-lutein cells.

Ascorbic acid serves a vital role as a pre-eminent antioxidant. In animals, it has been shown to be concentrated in granulosa and theca cells of the follicle, in luteal cells of the corpus luteum, and in the peripheral cytoplasm of the oocyte. We have previously identified hormonally-regulated ascorbic acid transporters in rat granulosa and luteal cells, and herein present preliminary evidence for the presence of a transporter for ascorbic acid in human granulosa-lutein cells. Granulosa-lutein cells were obtained from the follicular fluid of patients undergoing in-vitro fertilization. Following an overnight incubation, the cells were incubated with [14C]-ascorbic acid (0.15 microCi; 150 microM) and ascorbic acid uptake was determined. The uptake of ascorbic acid was saturable with a Michaeli's constant (Km) and maximum velocity (Vmax) of 21 microM and 3 pmol/10(6) cells/min respectively. Ouabain, low Na+ medium, and dinitrophenol significantly inhibited ascorbic acid uptake (P<0.05). Neither the presence of insulin, human chorionic gonadotrophin (HCG), insulin-like growth factor (IGF)-I, nor IGF-II affected the uptake of ascorbic acid in a statistically significant fashion. Following saturation of cellular uptake, the ascorbic acid level was estimated to be 1.04 pmoles/10(6) cells or approximately 1 mM, a high concentration similar to that seen in rat luteal cells. Active ascorbic acid transport in human granulosa-lutein cells appears to occur via a Na+ - and energy-dependent transporter, with high levels of ascorbic acid being accumulated in these cells.

Laparoscopic hernias: two case reports and a review of the literature.

Laparoscopic operations are becoming more common and replacing more traditional surgical procedures. As a result, radiologists should be aware of some of the unique complications that may occur from these types of procedures. We report two cases of incarcerated bowel hernias in lateral trocar sites.

A case of fatal pulmonary thromboembolism associated with the use of intravenous estrogen therapy.

OBJECTIVE: To report a case of fatal pulmonary embolism associated with the use of i.v. estrogen therapy for menometrorrhagia. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 52-year-old woman with fibroid uterus treated with GnRH analogues with add-back therapy who presented with excessive vaginal bleeding. INTERVENTION(S): Intravenous conjugated estrogens were administered for a total of six doses. MAIN OUTCOME MEASURE(S): Fatal thromboembolic event. RESULT(S): The day after i.v. conjugated estrogens were administered, the patient had only scant vaginal bleeding, but she experienced the sudden onset of respiratory distress, became comatose, and subsequently had ventricular fibrillation leading to asystole. All resuscitative efforts failed. Postmortem examination revealed bilateral pulmonary artery thromboembolism (saddle embolus). CONCLUSION(S): Intravenous conjugated estrogen therapy may be complicated by fatal thromboembolic events. This potential adverse effect must be considered in the use of such therapy for severe menometrorrhagia, especially when treating a patient at increased risk.

Unicornuate uterus with a rudimentary horn and ovarian dysgerminoma. A case report.

BACKGROUND: Several documented cases of endometrial and cervical carcinoma arising in unicornuate uteri have been described; however, ovarian malignancy occurring in conjunction with this müllerian anomaly has not been reported. CASE: An 18-year-old woman had a unicornuate uterus, noncommunicating rudimentary horn and homogeneous, solid, right ovarian mass found to be a dysgerminoma at surgery. CONCLUSION: Müllerian anomalies are unlikely to predispose women to ovarian malignancies. However, it is essential to keep in mind that women with such anomalies, though presenting at a young age, could still have cervical, uterine or even ovarian malignancies.

Cryomyolysis in the management of uterine fibroids: technique and complications.

Uterine fibroids are common benign tumors of the uterus and a major public health problem. Between 20 and 25% of women over 35 years of age are estimated to have fibroids. Three subtypes of fibroids are recognized depending on their relationship to the myometrium, namely, submucosal, subserosal and intramural. Fibroids are frequently asymptomatic, but may be associated with menorrhagia, dysmenorrhea, pregnancy loss or infertility. They are composed predominantly of smooth muscle, with a variable amount of connective tissue, and they have a characteristic smooth white whorled appearance on cross sectional examination.

Myometrial tissue in uterine septa.

STUDY OBJECTIVE: To assess the frequency of myometrial tissue in the septa of septate uteri. DESIGN: Retrospective review (Canadian Task Force classification II-2). SETTING: University-affiliated tertiary referral center. PATIENTS: Twenty-nine consecutive women with uterine septa diagnosed by magnetic resonance imaging (MRI). INTERVENTIONS: The MRI examination was performed with a 1.5 Tesla scanner using high-resolution phased array coils with multiplanar fast-spin echo and T1-weighted sequences. Of resected septa, tissue was available in four for histologic evaluation for the presence of myometrial tissue. MEASUREMENTS AND MAIN RESULTS: In 17 women MRI showed a partial septum, all containing myometrium. The 12 patients with complete septum had evidence of myometrium in the upper part of the septum, with fibrous tissue constituting the lower part. Histology reviewed from four resected septa (2 partial, 2 complete) reported myometrial tissue. CONCLUSION: Uterine septa are frequently composed of myometrial tissue.

Endometrial cryoablation, a minimally invasive procedure for abnormal uterine bleeding.

STUDY OBJECTIVE: To evaluate the effectiveness of endometrial cyroablation for abnormal uterine bleeding. DESIGN: Prospective study with 22 months follow-up (Canadian Task Force classification II-2). SETTING: University Medical Center. PATIENTS: Fifteen consecutive patients treated for metrorrhagia or menorrhagia refractory to medical or surgical therapy, and who were either not operative candidates or did not desire hysterectomy. INTERVENTION: Cyroablation of the endometrium. MEASUREMENTS AND MAIN RESULTS: Fifteen patients underwent 16 procedures for dysfunctional uterine bleeding. Uterine sounding depth was 6 to 15 cm. One patient had spinal anesthesia, seven had general anesthesia, and seven had intravenous conscious sedation with a cervical block. Eight patients underwent cryosurgery while fully anticoagulated. Posttreatment endometrial biopsies were performed on three patients and showed only granulation tissue. Life table calculations give amenorrhea rates of 75.5% at 6 months and 50.3% at 22 months. One woman underwent a repeat procedure, resulting in hypomenorrhea at 7-month follow-up. CONCLUSION: This pilot study suggests that endometrial cryoablation may be performed simply and effectively. Future studies should be designed to optimize the technical aspects of the procedure, determine its relative efficacy, and investigate the indications.

Cryomyolysis, a new procedure for the conservative treatment of uterine fibroids.

Conservative surgical options for uterine myomata traditionally were abdominal myomectomy, laparoscopic myomectomy, and, more recently, myolysis. Each of these procedures has distinct advantages, but also apparent disadvantages. We attempted to introduce an additional option for conservative surgical treatment of fibroids by freezing the structures, a procedure termed cryomyolysis. In this pilot study, 14 women were pretreated with a gonadotropin-releasing hormone (GnRH) agonist for a minimum of 2 months preoperatively to minimize uterine and myoma size. Cryomyolysis was performed and the GnRH agonist was discontinued. Magnetic resonance imaging scans were performed in 10 of the 14 women after GnRH agonist treatment but before surgery, and 4 months postoperatively. Total uterine volume ranged from 41.3 to 1134.8 ml preoperatively, and 49.5 to 1320 ml postoperatively (mean increase 22% after discontinuation of GnRH agonist). Normal uterine volume ranged from 35.6 to 548.7 ml preoperatively and 45.1 to 729.6 ml postoperatively (mean increase 40%); however, myoma volume showed a mean decrease of 6% (range -87-28%). Analysis of only frozen myomata revealed a mean volume decrease of 10%. Cryomyolysis maintains at or slightly reduces these lesions to post-GnRH agonist size, and all other uterine tissue returns to pretreatment size. We believe cryomyolysis may be an effective conservative surgical approach to uterine fibroids.

Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells.

The peritoneal environment in endometriosis is known to have growth-promoting effects on endometrial cells. To investigate whether follicular fluid, a contributor to the peritoneal fluid, stimulates endometrial cell proliferation, we incubated endometrial stromal cells in culture with various dilutions of follicular fluid obtained from women with or without endometriosis undergoing oocyte retrieval for in-vitro fertilization. Cell proliferation assays were performed using follicular fluid from 28 women (without endometriosis, n = 13; with endometriosis, n = 15) in eight different endometrial stromal cell culture set-ups. Cell proliferation was assessed by a colorimetric method. Maximum cell proliferation was detected when endometrial cells were incubated with 50% dilution of follicular fluid for 48 h. Follicular fluid from women with endometriosis induced significantly higher cell proliferation than follicular fluid from women without endometriosis (P < 0.05). Our findings indicate that follicular fluid contents may contribute to the growth-promoting factors in the peritoneal fluid of women with endometriosis.

Pathophysiology. The biologic principles of disease.

Endometriosis, although associated with a large variety of symptoms, primarily produces pain and infertility; however, the strong correlation with these disorders, along with basic questions as to why endometriosis develops, when does it become a disease status, and why it's associated with symptoms such as pain or infertility, are still not well understood. A better understanding of the relationship between disease and symptoms of endometriosis must be acquired if effective progress in the treatment of pain and infertility related to endometriosis is to be made.

Hormone induction of ascorbic acid transport in immature granulosa cells.

Ascorbic acid serves a vital role as an antioxidant, and like FSH, it inhibits apoptosis of granulosa cells in cultured follicles. In contrast, reactive oxygen species block the action of FSH and induce DNA damage in these cells. As the uptake of ascorbic acid by granulosa cells may be a site for regulation, we examined the nature of this process and whether uptake is under hormone control. Granulosa cells were isolated from immature rats pretreated with estradiol or diethylstilbestrol for 3-4 days and placed in culture. Culture of the cells with either FSH (50 ng/ml) or insulin-like growth factor I (IGF-I; 30 ng/ml) for 48 h increased ascorbic acid uptake by 2.7- and 1.9-fold (P < 0.05), respectively, and the response to FSH plus IGF-I was additive (4.5-fold; P < 0.05). The interval for maximum induction of ascorbic acid transport by FSH was between 4-8 h, whereas a significant response to IGF-I was not seen until 48 h. GnRH (1 microM), phorbol ester (phorbol 12-myristate 13-acetate; 1 microM), and 8-bromo-cAMP (8Br-cAMP; 1 mM) also induced ascorbic acid transport by 1.7-, 1.9-, and 2.3-fold (P < 0.05) within 24 h, and the response to maximal levels of phorbol ester and 8Br-cAMP was synergistic (4.8-fold; P < 0.05). Kinetic analysis showed a similar Michaelis constant (K(m); 50.8 +/- 5.3 microM) and maximum velocity (3.3 +/- 0.4 pmol/10(6) cells.min) for ascorbic acid transport in FSH-, 8Br-cAMP-, or phorbol ester-treated cells. Ouabain (100 microM) or removal of extracellular Na+ significantly inhibited ascorbic acid uptake, as did dinitrophenol (1 mM), an inhibitor of mitochondrial production of ATP. The induction of ascorbic acid transport by FSH, IGF-I, or GnRH was abolished by simultaneous incubation with tyrphostin (AG-18; 80 microM), a specific tyrosine kinase inhibitor, whereas induction was unaffected by an inactive, but chemically similar, compound (A-1; 80 microM). From these results we conclude that ascorbic acid uptake is energy and Na+ dependent and that the induction of ascorbic acid transporters in granulosa cells occurs through multiple hormones that ultimately influence tyrosine-specific protein kinases. The hormone-dependent induction of ascorbic acid accumulation in granulosa cells appears to be an essential process for the development and maintenance of a viable follicle.

Transvaginal uterine cervical dilation with fluoroscopic guidance: preliminary results in patients with infertility.

PURPOSE: To assess efficacy of uterine cervical dilation performed with fluoroscopic guidance to treat patients with infertility who have cervical stenosis, false channels within the endocervical canal, or both. MATERIALS AND METHODS: Fifteen patients in whom infertility was diagnosed were referred because the uterine lumen could not be accessed. Three of the patients had endometriosis. With fluoroscopic guidance, the cervix was cannulated and the endocervical canal was dilated with an angioplasty balloon or with dilators. Five patients underwent simultaneous fallopian tube recanalization. Five of 15 patients who underwent dilation subsequently underwent in vitro fertilization for embryo transfer (IVF-ET) or intrauterine insemination. RESULTS: Four patients became pregnant. Of those four, one underwent IVF-ET and one underwent intrauterine insemination. Two patients became pregnant spontaneously. In the five patients who underwent IVF-ET or intrauterine insemination and in the remaining eight patients, the cervix could be easily cannulated up to 7 months after dilation. CONCLUSION: Dilation of the uterine cervix may provide options for treatment in selected patients with infertility. The effect of dilation on patients with other sequelae of cervical obstruction such as endometriosis remains uncertain.