Isolated abnormal strict morphology is not a contraindication for intrauterine insemination.

This study sought to investigate whether isolated abnormal strict morphology (<5% normal forms) and very low strict morphology (0-1% normal forms) affects pregnancy rates in intrauterine insemination (IUI). This was a retrospective study performed at an Academic Medical Center/Reproductive Medicine Center. Four hundred and eight couples were included for 856 IUI cycles. 70 IUI cycles were performed in couples with abnormal strict morphology and otherwise normal semen parameters. Outcomes were measured as clinical pregnancy rate per IUI cycle as documented by fetal heart activity on maternal ultrasound. Clinical pregnancy rate did not significantly differ between the group with abnormal strict morphology [11/70 (15.7%)] and the normal morphology group [39/281 (13.9%)]. Additionally, there was no significant difference between the pregnancy rate in the abnormal morphology group compared to that of our overall institutional IUI pregnancy rate [145/856 (16.9%)]. Furthermore, there was no significant difference between pregnancy rate in the very low morphology group [3/14 (21.4%)] compared to those with normal morphology or the overall IUI pregnancy rate. Patients with isolated abnormal strict morphology have clinical pregnancy rates similar to those with normal morphology for IUI. Even in those with very low normal forms, consideration of IUI for assisted reproduction should not be excluded.

TCDD increases inhibin A production by human luteinized granulosa cells in vitro.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic of the halogenated dioxins and one of the most poisonous substances known to man. The major toxic effects of TCDD on reproduction are decreased fertility and diminished ability to maintain a pregnancy. Granulosa cells obtained from hormonally stimulated women participating in an in-vitro fertilization program were cultured with 3.1 femtomolar, 3.1 picomolar and 3.1 nanomolar TCDD. While inhibin B production was not altered, inhibin A production increased significantly after 4 hours of exposure to both nanomolar and micromolar TCDD concentrations. By 8 hours of exposure to these concentrations of dioxin, human luteinizing granulosa cells exhibited a pronounced increase in inhibin A, nearly quadrupling secretion from unexposed control cells. TCDD continued to increase inhibin A secretion at the picomolar concentration at 24 and 36 hours. It is conceivable that TCDD may act at the ovary to augment inhibin A secretion, thereby reducing FSH-stimulable estrogen secretion by granulosa cells.

Minimal precycle testing and ongoing cycle monitoring for in vitro fertilization and fresh pre-embryo transfer do not compromise fertilization, implantation, or ongoing pregnancy rates.

OBJECTIVE: We sought to assess the fertilization, implantation, and ongoing pregnancy rates with a minimal precycle and ongoing cycle monitoring protocol for in vitro fertilization and embryo transfer. STUDY DESIGN: Retrospective review was conducted of 103 consecutive cycles of fresh in vitro fertilization and embryo transfer from 1996 to 1998. Precycle screening included semen analysis without strict morphologic analysis, and hysterosalpingography-sonohysterography within the last year. Serum prolactin, serum thyroid-stimulating hormone, reactive plasma reagin, human immunodeficiency virus, rubella titer, blood type, hepatitis B surface antigen, and hepatitis C antibody testing was performed on all patients within 3 months of cycle initiation. Women > or =37 years old underwent clomiphene challenge testing. The monitoring protocol included the following: baseline transvaginal ultrasonography after 12 to 14 days of midluteal gonadotropin-releasing hormone agonist down-regulation to assess endometrial thickness and adnexal appearance, transvaginal ultrasonography for follicle evaluation at 7 and 10 days, serum estradiol assay if > or =20 follicles, quantitative beta-human chorionic gonadotropin 12 to 14 days after pre-embryo transfer, repeat quantitative beta-human chorionic gonadotropin 3 to 5 days later, and transvaginal ultrasonography for intrauterine gestational sac confirmation 7 to 9 days after the initial positive pregnancy test result. The dose of gonadotropin used remained constant unless the sonogram obtained on day 7 indicated a suboptimal response (<3 follicles each, with an average diameter of 10 to 12 mm) or hyperresponse (> or =15 follicles with an average diameter of 10 to 12 mm). RESULTS: The per embryo implantation rate (fetal cardiac activity) was 13.1%, and the live birth rate per 100 pre-embryo transfers was 31.5 for patients < or =40 years old. The average number of pre-embryos transferred was 3.1. The singleton pregnancy rate was 71%, and there were no multiple gestations greater than twins. The mean number of oocytes fertilized was 66%. There was 1 case of failed fertilization with intracytoplasmic sperm injection. There were two other cases of failed fertilization. One case of severe ovarian hyperstimulation occurred in spite of cryopreservation of all embryos. CONCLUSIONS: In vitro fertilization and embryo transfer can be accomplished with minimal precycle testing and ongoing cycle monitoring without compromising fertilization, implantation, and ongoing pregnancy rates. This results in reduced overall costs for couples.

Laparoscopic resection of sigmoid endometrioma.

Endometriosis as a cause for pelvic pain is quite common in women of child-bearing age. However, colonic an rectal involvement is relatively rare and may have a wide array of clinical symptomatology and radiographic findings. We recently treated a patient who presented with constipation and bloating. She was found to have an extrinsic mass compressing the rectosigmoid junction. Subsequent diagnostic laparoscopy revealed a large lesion involving the sigmoid colon, and resection with primary anastomosis was performed using the laparoscope. Final pathology revealed benign endometrioma. The patient did well, was discharged on postoperative Day 3, and has had no further complaints. As this case shows, laparoscopy can be beneficial in both the diagnosis and treatment of patients with intestinal endometriosis.

Insulin-like growth factor I promotes leiomyoma cell growth in vitro.

OBJECTIVE: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture. STUDY DESIGN: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture. RESULTS: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factors II. Neither factor exerted a stimulatory effect on myometrial cells. CONCLUSION: Insulin-like growth factors I preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracrine role in vivo for this factor in conjunction with gonadal steroids in promoting leiomyoma growth.

Estrogen receptor gene expression in human uterine leiomyomata.

Estrogen and progestin are believed to be important physiological regulators of uterine leiomyoma growth. We recently showed that progesterone receptor messenger ribonucleic acid (mRNA) and protein levels are increased in human uterine leiomyomas compared with those in myometrial biopsy tissue obtained from the same patient. To further characterize the molecular mechanisms underlying abnormal growth of uterine leiomyomas, we analyzed biopsy samples of tumor and adjacent normal myometrium for estrogen receptor (ER) gene expression. Northern analysis indicated that ER mRNA levels were increased 1.4-to 12.6-fold in leiomyoma compared with myometrium in all patients examined (n = 11), whereas beta-actin mRNA was not different between the two groups. The size of the primary ER mRNA transcript was 6.2 kilobases in both leiomyoma and myometrium, indicating no gross mutation of the ER gene. An ER protein of 66 kilodaltons was detected by Western blot analysis, and quantitative immunoassay of ER revealed 9448 +/- 1955 fmol/mg DNA in leiomyoma compared to 2827 +/- 979 fmol/mg DNA in myometrial tissue. Scatchard analysis of 17 beta-estradiol binding to cell-free extracts revealed enhanced binding capacity (per mg DNA) in leiomyoma tissue (n = 6) of about 6-fold, whereas ER binding affinity was not substantially different between the leiomyoma and adjacent myometrial tissues. We propose that increased expression of progesterone receptor in leiomyoma is most likely a consequence of overexpression of functional ER that results in increased end-organ sensitivity to estradiol.

Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyomas.

OBJECTIVE: Our purpose was to identify molecular mechanisms underlying abnormal growth of uterine leiomyomas. STUDY DESIGN: Biopsy samples of tumor and adjacent "normal" myometrium from nine patients were analyzed for progesterone receptor gene expression and for proliferation-associated antigen Ki-67. RESULTS: Northern analysis indicated that progesterone receptor messenger ribonucleic acid levels were increased twofold to 15-fold in leiomyoma compared with adjacent myometrial biopsy tissue from all patients (n = 9), whereas beta-actin messenger ribonucleic acid was at similar levels in these samples. Quantitative immunoassay, immunohistochemistry studies, and Western blot analyses revealed increased amounts of progesterone receptor protein in the tumor tissue. Both the progesterone receptor A and B forms were expressed in the leiomyoma and adjacent myometrium. Corresponding to increased progesterone receptor gene expression, the proliferation-associated antigen Ki-67 was also significantly elevated in the leiomyoma tissue. CONCLUSION: These data provide the first evidence that progesterone receptor messenger ribonucleic acid is overexpressed in uterine leiomyomas, suggesting that amplified progesterone-mediated signaling is instrumental in the abnormal growth of these tumors.

Pathophysiology of the ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome occurred after induction of ovulation with menotropins (follicle-stimulating hormone and luteinizing hormone) and implantation of an intrauterine pregnancy. Serial determinations of aldosterone, deoxycorticosterone, 17 beta-estradiol, progesterone, human chorionic gonadotropin, urinary and plasma electrolytes, and fluid balance were obtained. Plasma renin activity, aldosterone, deoxycorticosterone, and antidiuretic hormone rose markedly. Hydration for four days improved urinary output but also accelerated sodium and fluid retention. Subsequent restriction of salt and water stabilized the patient. Spontaneous abortion was followed by prompt diuresis without a change in therapy. Regression analysis of the authors' data, the clinical observations, and other data in the literature suggest that the ovarian hyperstimulation syndrome is produced by excessive secretion of an unknown hormone that regulates peritoneal fluid during the normal menstrual cycle, and that elevations of plasma renin, aldosterone, and antidiuretic hormone are secondary.