Bryan R. Hecht

Tranexamic Acid Treatment for Heavy Menstrual Bleeding: A Randomized Controlled Trial

OBJECTIVE: To assess the efficacy and safety of an oral formulation of tranexamic acid for the treatment of heavy menstrual bleeding. METHODS: Adult women with heavy menstrual bleeding (mean menstrual blood loss 80 mL or more per cycle) were enrolled in a double-blind, placebo-controlled study. After two pretreatment menstrual cycles, women were randomized to receive tranexamic acid 3.9 g/d or placebo for up to 5 days per menstrual cycle through six cycles. To meet the prespecified three-component primary efficacy end point, mean reduction in menstrual blood loss from baseline with tranexamic acid treatment needed to be 1) significantly greater than placebo, 2) greater than 50 mL, and 3) greater than a predetermined meaningful threshold (36 mL or higher). Health-related quality of life was measured using a validated patient-reported outcome instrument. RESULTS: Women who received tranexamic acid (n=115) met all three primary efficacy end points: first, a significantly greater reduction in menstrual blood loss of −69.6 mL (40.4%) compared with −12.6 mL (8.2%) in the 72 women who received placebo (P<.001); reduction of menstrual blood loss exceeding a prespecified 50 mL; and last, reduction of menstrual blood loss considered meaningful to women. Compared with women receiving placebo, women treated with tranexamic acid experienced significant improvements in limitations in social or leisure and physical activities, work inside and outside the home, and self-perceived menstrual blood loss (P<.01). The majority of adverse events were mild to moderate in severity, and the incidence of gastrointestinal adverse events was comparable with placebo. CONCLUSION: In this study, a new oral tranexamic acid treatment was well tolerated and significantly improved both menstrual blood loss and health-related quality of life in women with heavy menstrual bleeding. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00386308. LEVEL OF EVIDENCE: I

Comparison of the methods of artificial insemination on the incidence of conception in single unmarried women.

OBJECTIVE To compare pregnancy rates after intrauterine insemination (IUI) versus pericervical insemination in absolute male factor infertility using each patient as her own control. DESIGN Ovulatory women with patent fallopian tubes without male partners were alternately inseminated with cryopreserved donor semen using either IUI or pericervical insemination techniques. A total of 81 cycles, which included up to 4 cycles per patient were performed. In this manner a comparison between the efficacy of each method could be evaluated. SETTING The donor insemination program at the Center For Assisted Reproduction at Northwestern University Medical School. PATIENTS Twenty-six single, healthy, unmarried women with patent fallopian tubes and < 40 years of age without male partners (absolute male factor infertility). MAIN OUTCOME MEASURES Positive quantitative serum subunit of human chorionic gonadotropin followed by the presence of an intrauterine gestational sac seen by transvaginal ultrasonography. RESULTS Fourteen (54%) of 26 patients conceived including two (14%) miscarriages within four insemination cycles. Seven (17.5%) patients after IUI, and 7 (17.1%) patients after pericervical insemination conceived. The pregnancy rates were similar regardless of the order of insemination method. CONCLUSION These findings reveal that there is no statistical difference in the pregnancy outcome between these two methods of insemination in absolute male factor infertility.

Luteal insufficiency: Correlation between endometrial dating and integrated progesterone output in clomiphene citrate-induced cycles

Midluteal phase endometrium was histologically dated with midcycle luteinizing hormone surge time in 29 cycles from 10 parous women during untreated cycles (control) and treatment with clomiphene citrate 50 mg and 150 mg daily on days 5 through 9. Integrated progesterone output for 7 days after luteinizing hormone surge calculated from the daily plasma progesterone levels was 66.6 +/- 9.8 ng/ml in the control group compared with 117.5 +/- 18.6 ng/ml for clomiphene citrate 50 mg treatment and 152.1 +/- 11 ng/ml for clomiphene citrate 150 mg treatment (p less than or equal to 0.05). Only one cycle (clomiphene citrate 150 mg) had an out-of-phase endometrium and a significantly reduced integrated progesterone output of 28 ng/ml. All other cycles showed synchronous endometrial maturation. We conclude that luteal insufficiency as a result of clomiphene citrate treatment in ovulatory women is infrequent and is more likely to be a result of functional outcome of a relative lack of luteal phase progesterone output.

Strategies for ovulation induction and oocyte retrieval in the lowland gorilla

Purpose: Ovulation induction and oocyte retrieval were performed in a lowland gorilla in an attempt to propagate and potentially cryopreserve embryos from an infertile animal and to advance techniques to help preserve this endangered species.Results: Following 34 days of leuprolide acetate suppression, human menopausal gonadotropins were administered for 14-days in a 32-year-old wild-born lowland gorilla. Ten oocytes were retrieved by transrectal ultrasound-guided aspiration. Other approaches to oocyte recovery were not feasible in this case. A serum estradiol concentration of 4700 pg/ml at the time of human chorionic gonadotropin administration did not induce ovarian hyperstimulation. Mature oocytes were recovered from follicles measuring 14 to 24 mm in diameter, with a corresponding average serum estradiol concentration of approximately 300 pg/ml for each mature follicle. Cryopreservation of a gorilla embryo was effected from cryopreserved gorilla spermatozoa.Conclusions: Parameters for monitoring ovulation induction in the gorilla appear to be similar to those for humans. The results indicate that the use of a gonadotropin releasing hormone agonist and higher doses of gonadotropins than previously used in gorillas appear to improve oocyte recovery.

Salpingitis or oophoritis: What causes fever following oocyte aspiration and embryo transfer?

Background: Febrile morbidity following in vitro fertilization and embryo transfer (IVF-ET) is a rare but possibly serious complication. This report describes a case of salpingitis after IVF-ET and discusses the possible reasons for febrile morbidity following this common procedure. Case: A 37-year-old woman undergoing IVF-ET for tubal factor infertility developed sudden, severe pelvic pain, fever, and leukocytosis 24 hours after ET. Laparoscopy revealed bilateral suppurative pyosalpinges with cystic, hemorrhagic ovaries. Pain, fever, and leukocytosis resolved with conservative surgery and intravenous antibiotic therapy. Conclusions: This case presents laparoscopic documentation of a rare complication of oocyte aspiration and/or ET, namely, salpingitis. Possibilities for the development of salpingitis following IVF-ET include activation of quiescent bacteria within the fallopian tubes from a previous pelvic infection, puncture of the bowel during oocyte aspiration, inoculation of the pelvis with cervicovaginal flora during oocyte aspiration, and introduction of bacteria-laden secretions or air into the fallopian tubes during ET. Although rare, the possibility of severe pelvic infection following IVF-ET warrants consideration of prophylactic antibiotic coverage. (Obstet Gynecol 1993;81:876–7)

The straw swim-up: a simple method to evaluate the effects of additives, media, or toxicants on sperm motility**Presented at the 47th Annual Meeting of The American Fertility Society, Orlando, Florida, October 21 to 24, 1991.

We describe a new method for evaluating potential toxicants, spermicides, and motility enhancers. Cryopreservation straws filled with media plus additive are emersed below the surface of an unprocessed donor ejaculate. After incubation, the sperm found within the first 4 cm of the straw are expelled and analyzed. The effects of media containing glycerol and albumin were examined. Survivability and sperm migration into the media occur independently and can be differentiated in this assay. This method allows for the use of unprocessed semen and includes an evaluation of the semen and media interaction.