Doppler and gray-scale sonographic classification of adnexal torsion.

OBJECTIVE: To propose, in cases with coiling of the ovarian vessels, a classification of severity of torsion based on Doppler and gray-scale ultrasound findings and to suggest a treatment strategy for each situation. METHODS: Seventeen patients were examined in a gynecological emergency room between December 1995 and February 2003 due to suspected adnexal torsion. Doppler and gray-scale ultrasound were used to visualize coiling of the ovarian blood vessels. Intraovarian flow was assessed by spectral Doppler and on this basis, along with the patient's clinical condition, the decision was made as to whether surgery was necessary. Findings on surgery were recorded. RESULTS: All 17 patients showed coiling of the ovarian vessels. Nine had arterial and venous blood flow within the ovary and ultrasound and surgical findings usually demonstrated normal sized or mildly enlarged ovaries. Five had only arterial blood flow within the ovary and surgery usually revealed enlarged ovaries with normal color or mild discoloration. Three had neither arterial nor venous blood flow within the ovary, with vessel coiling evident only on gray-scale and not on Doppler examination, and surgical findings included signs of ovarian ischemia or necrosis. CONCLUSION: In cases of coiling of the ovarian vessels, Doppler flow analysis of the ovary can help differentiate between ischemic adnexal torsion and coiling of the ovarian blood vessels without strangulation, aiding in the choice of treatment. According to type of blood flow seen on Doppler examination, we suggest the following classification of severity of adnexal torsion and treatment strategy: Class 1, coiling with arterial and venous ovarian blood flow; a conservative approach may be considered if the clinical condition permits; Class 2, coiling with arterial ovarian flow but no venous flow; surgical intervention is required; and Class 3, true strangulation, with no ovarian blood flow; urgent surgical intervention is required.

Vaginal evisceration long after vaginal hysterectomy.

BACKGROUND: Vaginal evisceration can take place many years after vaginal surgery. CASE: An 87-year-old woman presented with evisceration of small bowel through the vagina, 15 years after she underwent a vaginal hysterectomy. On physical examination, her vital signs were normal. Forty centimeters of small bowel was visible emerging from the vagina, appearing viable and nonedematous. Because of the high surgical risk, the bowel was replaced and the defect in the vaginal wall was repaired transvaginally. CONCLUSION: Vaginal evisceration can be treated by a transvaginal surgical approach. Factors such as the medical condition of the patient and the viability of the herniated viscus should dictate the optimal approach in each case.

Endometrial ablation for the postmenopausal woman.

The postmenopausal woman with abnormal uterine bleeding is considered at risk for developing endometrial neoplasia or one of its precursors. She requires prompt evaluation of the endometrium followed by adequate treatment. In the subgroup of postmenopausal women taking hormone replacement therapy (HRT), the risk of abnormal bleeding is by far higher, is the main reason for discontinuing HRT, and deserves additional attention.

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.

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.

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)

Follow-up of small, postmenopausal ovarian cysts using vaginal ultrasound and CA-125 antigen.

To determine the natural history of small, simple ovarian cysts in postmenopausal women, 51 postmenopausal patients with small (< 5 cm), smooth, aseptate, hypoechogenic ovarian cysts, without ascites, were followed by vaginal ultrasound examinations every 3 months for an average period of 2.5 years. In 34, CA-125 antigen was measured and found to be within normal limits. None of the cysts showed changes in texture, nor did ascites appear. The CA-125 antigen serum levels remained low. The mean size of the cysts decreased with time. There was no statistically significant correlation between the initial size of the cyst, its tendency to grow or shrink, and the absolute CA-125 serum level. Our findings support the option of a conservative follow-up by repeated ultrasonic and CA-125 antigen examinations of small, simple cysts in postmenopausal women.

Functional differentiation in progesterone secretion by granulosa versus cumulus cells in the human preovulatory follicle and the effect of different induction of ovulation protocols.

OBJECTIVE: To investigate P secretion by granulosa cells (GCs) versus cumulus cells derived from human preovulatory follicles. DESIGN: Cells were recovered by aspiration of preovulatory follicles in 44 women participating in an IVF program. Induction of ovulation was performed using clomiphene citrate, hMG and hCG (group I), hMG/hCG (group II), buserelin acetate/hMG/hCG (group III), or Decapeptyl/hMG/hCG (group IV). SETTING: Laboratories of the IVF Unit at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. MAIN OUTCOME MEASURES: Secretion of P was examined after cultures for 96 hours under nonstimulated and hCG stimulated conditions. RESULTS: Progesterone secretion by GCs derived from all four groups was found to be higher compared with the respective cumulus cells. However, although the ratios of P secretion by GCs versus cumulus cells in groups I, II, and III were very similar, a significantly lower value was observed in group IV. The response of GCs to hCG in terms of P secretion was higher with at least one dose of hCG in groups I and IV compared with groups II and III. The response of cumulus cells to hCG was absent regardless of the treatment protocol used in vivo. CONCLUSION: Our results demonstrate that in the human preovulatory follicle, GCs and cumulus cells differ in their capacity to secrete P as well as in their response to hCG. They further suggest that the mode of induction of ovulation affects the relative capacity of GCs and cumulus cells to secrete P and their ability to respond to hCG.

Gamete intrafallopian transfer. An overview.

Gamete intrafallopian transfer involves a direct transfer of both human gametes, sperm and oocytes, into the fallopian tube. Since the first report of a successful pregnancy following the use of this technique by Asch et al in 1984, its role in the treatment of infertile women with patent tubes has been established. Recent data demonstrate a 34.4% clinical pregnancy rate, with the highest pregnancy rate achieved in infertile women due to endometriosis or unexplained infertility.

The effect of epidermal growth factor on growth and differentiation of mouse preimplantation embryos in vitro.

The effect of epidermal growth factor (EGF) on embryonic growth, development, attachment and spreading in vitro was studied. EGF was added to 130 embryos at the 4-cell stage; to 128 embryos at the blastocyst stage; and to 147 embryos 24 h following spreading. Development of embryos from the 4-cell to the blastocyst stage, differentiation of the inner cell mass (ICM) and trophectoderm, and the occurrence of attachment and spreading were evaluated. Embryo development was significantly inhibited in cultures supplemented with 100 ng/ml EGF compared to the controls (P < 0.001). Development of 4-cell embryos to blastocysts occurred in 25% of the EGF group compared to 85% of controls. Spreading occurred in 20% of 4-cell embryos and 30% of blastocysts treated with EGF, compared to 80 and 90% of corresponding controls. In embryos developing from the 4-cell stage, massive growth of the ICM and inhibition of the trophectoderm occurred, whereas both ICM and trophectoderm were inhibited by EGF in embryos developing from the blastocyst stage. Following spreading, EGF caused massive growth of the ICM and regression of the trophectoderm. Our preliminary results show that EGF may be involved in the modulation and control of early embryonic growth and differentiation.

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.

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.

PURPOSE: Our 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). PATIENTS: Only 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). SETTING: The setting was the IVF program at Carmel Medical Center, Haifa, Israel. RESULTS: The 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). CONCLUSIONS: Our 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.

Use of a sealed mini-chamber to investigate human sperm motility in real time under aerobic and anaerobic conditions.

To study the correlation between metabolism and motility, ejaculated human spermatozoa were washed in media containing glucose, pyruvate, and deoxyglucose in various combinations. Spermatozoa suspended in these media were incubated in sealed mini-chambers and subjected to aerobic or anaerobic conditions at 37 degrees C. The effect on the patterns of sperm motility was investigated in real time by direct observation and objective determination with the multiple exposure photography (MEP) method. The motility of spermatozoa incubated in media containing excess of glucose showed similar changes of motility quality with time, whether exposed to aerobic or anaerobic conditions, and in both cases motility lasted about 13 h. Motility of sperm incubated with pyruvate only was of a much lower quality, especially under anaerobic conditions, and in both circumstances lasted about 7 h. When glycolysis of fructose remnants was totally inhibited by deoxyglucose and sperm were incubated with pyruvate only, motility lasted for 2 h under aerobic conditions and only for about 1 h under anaerobic conditions. It is concluded that the main metabolic process that supplies energy for sperm motility is glycolysis, under both aerobic and anaerobic conditions. Oxidative respiration was less efficient as a source of energy for sperm motility. When glycolysis was inhibited and oxidative respiration was eliminated under anaerobic conditions, sperm motility lasted only for about 1 h, probably by using intracellular energy reserves.

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 less than 0.01). Cancellation rate was significantly lower in Group I than in Group II (P less than 0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos transferred 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.

The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome.

Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins.

Oral contraceptive pills and follicular fluid hormones in an in vitro fertilization program.

Fluids were collected from 136 ovarian follicles of 35 women undergoing in vitro fertilization and embryo transfer (IVF-ET). Fifteen women (76 follicles) received oral contraceptive pills (OCs) prior to ovulation induction. All women received human menopausal gonadotropins (hMG) for ovulation induction and in all cases follicular aspiration was performed 32 to 34 hours after an injection of human chorionic gonadotropin (hCG). The concentrations of follicular-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and 17 beta-estradiol (E2) in the follicular fluids (FF) were measured by radioimmunoassay (RIA). FSH concentration in the FF of the OCs group (15 women, 76 follicles) was significantly lower (2.1 mIU/mL) as compared to the FSH (15.9 mIU/mL) in the FF of the control group (20 women, 60 follicles). The LH FF concentrations after hCG injection were similar in the two groups. The E2/P ratio in the OCs group (9.6) was significantly lower than the E2/P ratio in the control group (20.6). OCs given to patients before induction of ovulation with hMG results in lower E2/P ratios and lower FSH concentration in the FF.

The fertilization and cleavage rates of eggs recovered from the cul-de-sac.

Five hundred ninety-one oocytes were laparoscopically recovered in 93 consecutive stimulated cycles. Fifty-three of the 591 oocytes were collected from the cul-de-sac in 39 cycles. The cul-de-sac-originated oocytes had fertilization and cleavage rates of 72 and 79%, respectively; these rates were similar to those achieved in oocytes originating from follicles. A significant decrease in the fertilization rate of cul-de-sac-originated oocytes was noticed in oocytes collected from the cul-de-sac 60 minutes or more after the beginning of the procedure. Oocytes collected from the cul-de-sac yielded 21% of the embryos transferred in cycles where some of the oocytes were recovered from the cul-de-sac. These findings indicate that repeated aspirations of the cul-de-sac may increase the number of embryos transferred.

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.