Gary N. Frishman

Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.

Predicting probabilities of pregnancy and multiple gestation from in vitro fertilization : A new model

Objective To develop a statistical model that adjusts for variation between patients and adequately predicts the observed distribution of pregnancies among singletons and multiple gestations of various orders. Methods All in vitro fertilization (IVF) cycles from the inception of the IVF program at Women and Infants Hospital on May 26, 1988, until December 31, 1993, were evaluated using logistic regression in selected subsets. Results A new cycle-one specific model uses three different probabilities: P1, the probability of pregnancy (predicted by age and total embryo score); P2/P1, the conditional probability of finding a second implantation in those who had become pregnant with at least one (predicted by total embryo score); and P3/P2, the conditional probability of finding a third implantation in those who had become pregnant with at least two (with no significant predictors). This is the first model to use these three adjusted probabilities. Conclusion P1 increases with increasing total embryo score but decreases with increasing age. P2/P1 increases with increasing total embryo score but does not depend on age. Embryo scoring is useful because the total embryo score is a better predictor of P1 and P2/P1 than the number of embryos alone. By using patient-specific information (age and total embryo score) and cycle-specific tables, an estimate of the probability of pregnancy and multiple gestation can be provided before embryo transfer.

Serum inhibin levels are lower in ectopic than intrauterine spontaneously conceived pregnancies

OBJECTIVEnTo determine if serum inhibin concentrations are lower in ectopic (EP) versus intrauterine pregnancies (IUPs) that are conceived spontaneously.nnnDESIGNnCase-control study.nnnSETTINGnAcademic clinical practice.nnnPATIENTSnSerum samples were obtained from 19 women who had EP confirmed at surgery and by pathology. For comparison, serum samples were collected from 24 women of similar chronological and gestational age with sonographic evidence of an IUP.nnnMAIN OUTCOME MEASUREnSerum dimeric inhibin-A, total inhibin, P, and hCG.nnnRESULTSnSerum total and dimeric inhibin concentrations in women with EP were < 60% of the concentrations for women with single IUPs. Total inhibin, but not dimeric inhibin-A, was elevated in maternal serum before week 8 of gestation relative to normal menstrual cycle levels.nnnCONCLUSIONSnSerum inhibin concentrations are lower in EP as compared with IUPs that are spontaneously conceived and the relative amounts of dimeric inhibin-A, B, and alpha inhibin subunit in maternal serum may change throughout gestation.

Relaxin secretion in in vitro fertilization pregnancies

OBJECTIVEnThis study was designed to determine whether the late luteal functional status of the corpora lutea in in vitro fertilization cycles alters the secretion of relaxin during pregnancy.nnnSTUDY DESIGNnAnalysis of serum relaxin, human chorionic gonadotropin, and steroid concentrations in sera of women with pregnancies viable beyond the twelfth week as a result of in vitro fertilization treatment was performed.nnnRESULTSnThe serum estradiol and progesterone concentrations decreased 5.5- and 4-fold from days 5 to 6 after human chorionic gonadotropin to days 11 to 13 after human chorionic gonadotropin, respectively. The serum relaxin concentration increased 8-fold between the 11- to 15-day interval and the 16- to 50-day interval after human chorionic gonadotropin and another 6-fold to the 51- to 90-day interval after human chorionic gonadotropin (all p < 0.01). Multiple linear regression analysis showed that the serum estradiol level 11 to 13 days after human chorionic gonadotropin and the serum human chorionic gonadotropin level 11 to 15 days after human chorionic gonadotropin were the most powerful paired predictors of the concentration of serum relaxin measured in the 11- to 15-day interval after human chorionic gonadotropin interval (R2 = 0.39, n = 50), the 16- to 50-day interval (R2 = 0.61, n = 51), and the 51- to 90-day interval (R2 = 0.55, n = 39).nnnCONCLUSIONnSecretion of relaxin is determined by an interaction of the late luteal functional status of the corpora lutea and the human chorionic gonadotropin secreted by the implanting pregnancy. These data allow for the hypothesis that inducing functional luteolysis by substituting one or more injections of luteinizing hormone for the human chorionic gonadotropin injection may decrease secretion of steroids, relaxin, and other factors from the corpora lutea during pregnancy, decreasing the risk of premature delivery in multiple gestations and the ovarian hyperstimulation syndrome.

hematosalpinx after methotrexate treatment of unruptured ectopic pregnancy

A large asymptomatic hematosalpinx followed single low-dose MTX treatment of an unruptured EP, a previously unreported complication. Management and implications are discussed.

Triplet tubal pregnancy treated by outpatient laparoscopic salpingostomy

To our knowledge, this represents the first case of a laparoscopically treated triplet EP and the first time that a double EP in the same tube was treated conservatively (with preservation of the tube). Multiple EPs may be more common than currently thought, and our report offers an alternative explanation for at least some cases of persistent EP after conservative surgical therapy. Finally, given the substantial cost savings and reduced postoperative recovery time associated with operative laparoscopy, when the patient is stable and the surgeon experienced, the laparoscopic approach should be tried, regardless of the number of EPs or their size.

Surgeon's cornerEctopic pregnancy in a cesarean-section scar: The patient >6 weeks into an ectopic pregnancy, underwent local treatment

Cesarean scar ectopic pregnancies may be difficult to diagnose and may result in uterine rupture or hysterectomy. Based on location and vascularity, especially in the presence of fetal cardiac activity, local treatment with transvaginal ultrasound-guided injection of methotrexate is an excellent option which also optimizes the chance for fertility preservation.

Ectopic pregnancy in a cesarean-section scar

Cesarean scar ectopic pregnancies may be difficult to diagnose and may result in uterine rupture or hysterectomy. Based on location and vascularity, especially in the presence of fetal cardiac activity, local treatment with transvaginal ultrasound-guided injection of methotrexate is an excellent option which also optimizes the chance for fertility preservation.