Arie Lissak

Polymorphism for mutation of cytosine to thymine at location 677 in the methylenetetrahydrofolate reductase gene is associated with recurrent early fetal loss

OBJECTIVE This study was undertaken to determine whether a cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase is associated with particular subtypes of recurrent unexplained spontaneous abortion. STUDY DESIGN The prevalences of cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase among 41 patients with recurrent unexplained spontaneous abortions and among 18 healthy control subjects were determined with polymerase chain reaction. RESULTS Homozygosity and heterozygosity for the cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase were observed at nonsignificantly different rates among patients and control subjects (9% and 48% versus 22% and 38%, respectively, P <.95). Among patients with recurrent unexplained spontaneous abortions both homozygosity and heterozygosity were associated with significantly increased prevalence of recurrent early fetal loss rather than with repeated anembryonic gestations (P <.0001). CONCLUSION The observation that polymorphism for the cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase is associated with repeated early fetal losses rather than with anembryonic gestations strengthens the argument for the role of hypercoagulability and abnormal uteroplacental vasculature in recurrent spontaneous abortion.

Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization

OBJECTIVE To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. DESIGN A prospective, randomized controlled trial. SETTING Hospital-based IVF Unit. PATIENT(S) Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. INTERVENTION(S) In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. MAIN OUTCOME MEASURE(S) Ovarian stimulation patterns and IVF outcome. RESULT(S) A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). CONCLUSION(S) Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.

A randomized prospective study on the effect of short and long Buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I—long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II—short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P<0.01). Cancellation rate was significantly lower in Group I than in Group II (P<0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos trans-ferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.

Immediate versus delayed treatment of perimenopausal bleeding due to benign causes by balloon thermal ablation.

STUDY OBJECTIVE To compare the effectiveness and safety of thermal balloon ablation without pretreatment with endometrium-thinning agents compared with delayed ablation with pretreatment for women with perimenopausal menorrhagia. DESIGN Prospective, randomized, controlled trial (Canadian Task Force classification I). SETTING Hospital-based ambulatory medical center. PATIENTS Thirty women age 46 to 51 years with severe enough perimenopausal menorrhagia to make them candidates for either hysterectomy or endometrial ablation. Two patients with submucosal myomas and six who had undergone cesarean section were included. INTERVENTIONS Thirteen patients were randomly assigned to be treated within 30 days and received a single intramuscular administration of gonadotropin releasing hormone (GnRH) analog; 17 women were allocated to be treated within 3 days of enrollment without uterine preparation. A thermal balloon was inserted transcervically under general anesthesia, and after inflation in the endometrial cavity with 5% dextrose in water, was heated to 87 degrees C for 8 minutes. MEASUREMENTS AND MAIN RESULTS Immediate and long-term major and minor complications and success rates were analyzed. Bleeding patterns and mean duration of menstrual flow were compared between groups at 6-month follow-up. No major intraoperative or postoperative complications occurred in either group, including the women who had recently undergone hysteroscopic myomectomy or had a history of cesarean section. Minor side effects were similar in both groups, and did not exceed 5%. Overall, at 6-month follow-up, 7 women were amenorrheic, 20 hypomenorrheic, and 3 eumenorrheic. No significant differences were noted between women treated with immediate or delayed ablation in either the distribution of bleeding patterns or days of flow per cycle (mean +/- SEM 1.8 +/- 0.42 vs 2.1 +/- 0.75 days, respectively). CONCLUSION This pilot study suggests that prompt treatment of perimenopausal menorrhagia with thermal balloon endometrial ablation is as effective and safe as deferred therapy combined with GnRH analog as an endometrium-thinning agent. In light of our results, the theory that previous cesarean section and presence of small submucosal myomas constitute relative contraindications for the procedure merits further consideration. (J Am Assoc Gynecol Laparosc 6(2):145-150, 1999)

A modest increase in serum progesterone levels on the day of human chorionic gonadotropin (hCG administration may influence pregnancy rate and pregnancy loss in in vitro fertilization-embryo transfer (IVF-ET) patients

PurposeOur purpose was to study the effect of a modest increase in preovulatory serum progesterone (P4) levels in hyperstimulated patients and its association with pregnancy rate and pregnancy loss following in vitro fertilization (IVF) and embryo transfer (ET).PatientsOnly patients with mechanical factor and three transferred embryos were included in the present study. They were divided into two groups according to two critical breakpoints for P4 serum levels on the day of hCG administration: serum P4 below 0.6 ng/ml in 28 cycles (group I) and >0.6 ng/ml in 80 cycles (group II).SettingThe setting was the IVF program at Carmel Medical Center, Haifa, Israel.ResultsThe pregnancy rate per embryo transfer was 53% (15/28) in group I and 10% (8/80) in group II (P < 0.025). Of 15 pregnancies achieved in group I, 14 were ongoing pregnancies, compared to 4 of 8 ongoing pregnancies in group II (P <0.03).ConclusionsOur findings suggest that a very modest increase in serum P4 levels on the day of hCG administration is associated with lower pregnancy and ongoing pregnancy rates in IVF-ET.

Treatment of hirsutism with cimetidine: a prospective randomized controlled trial *

Cimetidine (Tagamet, Smith Klein, Brussels, Belgium) the histamine receptor type 2 blocker, has been suggested as a possible treatment of hirsutism. In a prospective randomized controlled trial, cimetidine 1.5 gm a day was given for 3 months to 12 moderately or severely hirsute women, while 8 other women were randomized to serve as a control group. There was no significant change in the hair growth rate in either group as measured by two assessment methods. This finding suggests that cimetidine, given in the recommended dose for a period of 3 months, does not have a beneficial effect on hirsutism.

Different morphology and proliferative ability of cumulus and granulosa cells originating from cystic follicles aspirated from stimulated in vitro fertilization patients

OBJECTIVE To investigate the morphology and proliferative ability of cumulus and granulosa cells (GCs) originating from cystic follicles and normal-sized follicles after ovarian stimulation. DESIGN Granulosa cells, cumulus cells, and follicular fluid (FF) were aspirated from cystic follicles and normal-sized follicles from the same ovary. Morphology and proliferative ability of cumulus and GCs were assessed by Giemsa stain and thymidine incorporation, respectively. Cell proliferation was assessed in medium or FF originating from cystic follicles or normal-sized follicles. RESULTS An oocyte was found in 40% of the cystic follicles versus 68% in the normal-sized follicles. Changes in dispersion and adhesion properties were observed in cystic versus normal aspirated corona cumuli complex. Proliferative ability was consistently lower in GCs originating from cystic follicles versus normal-sized follicles. Proliferation of GCs originating from normal-sized follicles or cystic follicles was inhibited or increased when grown in FF from cystic follicles or FF from normal-sized follicles, respectively. Differences in embryo quality were significantly in favor of oocytes originating from normal-sized follicles. Although the fertilization rate of those oocytes appeared to be higher, the difference was not of statistical significance. CONCLUSIONS Inhibition of GC proliferation in FF from cystic follicles can be reversed by incubating cells in FF from normal-sized follicles. We conclude that factors in the FF may affect cell proliferation.

Pregnancies following the interval double-transfer technique in an in vitro fertilization-embryo transfer program.

SummaryIn 16 women undergoing IVF-ET, with more than four embryos available, two transfers were performed (24 hr apart), instead of one. The pregnancy rate was 25%, as compared with a pregnancy rate of 6.2% in 16 women having fewer than four embryos available and in whom one conventional transfer was performed.Since in our IVF-ET program, we do not freeze the extra embryos available, the purpose of the double transfer was to use all the embryos available and to improve the chances of finding the “implantation window” open.It is our feeling that multiple transfers may be beneficial to improve the pregnancy rate in an IVF-ET program without freezing facilities. However, a larger controlled clinical trial is necessary, in order to establish the advantages of multiple transfers in terms of pregnancy rate in comparison with the protential disadvantages.

Are women with pelvic organ prolapse at a higher risk of developing hernias

Introduction and hypothesisPelvic organ prolapse and hernia are common disorders which share several pathopysiological and epidemiological features. We therefore aimed to assess whether women with advanced pelvic organ prolapse have a higher prevalence of hernia.MethodsWe reviewed charts of women undergoing surgery for advanced pelvic organ prolapse and compared them to age-matched controls with mild or no prolapse.ResultsWe identified 60 patients who underwent surgery for advanced pelvic organ prolapse and 60 controls. The total prevalence of hernias was significantly higher among patients with pelvic organ prolapse (31.6% vs. 5%, p = 0.0002), attributed to hiatal (16.6% vs. 1.6%, p = 0.004) and inguinal (15% vs. 3.3%, p = 0.04) hernias.ConclusionsPatients with advanced pelvic organ prolapse have a higher prevalence of hiatal and inguinal hernias. This finding may be explained by similar pathophysiological mechanisms shared by both disorders.

Cystoscopy after total or subtotal laparoscopic hysterectomy: the value of a routine procedure

Ureteral injury during hysterectomy is one of the most troubling complications gynecologists need to be aware of. In various studies, such injury occurred in laparotomy, laparoscopy, and vaginal hysterectomy. The objective of our study was to assess the necessity, efficiency, and cost-effectiveness of cystoscopy at the end of total or subtotal laparoscopic hysterectomy (TLH/STLH). This is a retrospective analysis of 7 years’ experience in a university-affiliated hospital. All hysterectomies were performed on an overnight basis by experienced surgeons. Out of 338 patients, 106 patients underwent TLH, and 232 underwent STLH. Four cases (1.18%) of ureter injury were noted (one after TLH and three after STLH). Diagnosis was clinically made by postoperative vaginal sonography and was confirmed by intravenous pyelography. A cystoscopy was performed after intravenous indigo carmine injection. The study period consisted of two phases. In the first phase, we used bipolar cautery to occlude the uterine artery; consequently, a nearby thermal injury could be misdiagnosed. In the second phase we clipped the uterine artery with a new hemoclip called Hem-o-lok (Weck Closure Systems, USA), which forced an exact uterine artery closure. As a result, in the second phase no cases of ureteral injury were noted. In view of the fact that the equipment for cystoscopy is used during surgery for TLH/STLH and is sterile and available, the only additional cost of the cystoscopy is an ampule of indigo carmine. Therefore, we conclude that cystoscopy at the end of surgery for TLH/STLH is an important evaluation and provides the following significant advantages: In patients presenting with postoperative flank pain, cystoscopy may prevent the need for further evaluation and expensive testing, and cystoscopy increases the surgeon’s and the patient’s confidence in the integrity of the urinary tract during the recovery period.