Attitudes of Israeli gynecologists towards the levonorgestrel-releasing intrauterine system: a questionnaire survey.

OBJECTIVES: The aim of the study was to examine the current attitudes and practices of gynecologists regarding the use of the levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena, Schering AG, Germany) as a contraceptive device and for the treatment of menorrhagia in the premenopausal period. In addition, physician knowledge of patient satisfaction with the device was evaluated. METHODS: A written, self-administered questionnaire was given to 300 gynecologists actively employed in gynecological departments and outpatient clinics in urban centers in Israel. The items covered the indications for which the LNG-IUS was prescribed, the estimated rate of use of the LNG-IUS compared to copper intrauterine devices (IUDs), patient satisfaction with the LNG-IUS and previous knowledge about it, and demographic characteristics of the population using IUDs. All forms were completed on an anonymous basis. RESULTS: The questionnaire was returned, properly completed, by 298 physicians, yielding a response rate of 99.3%. Almost one-half of the physicians (n = 147, 49.3%) used the LNG-IUS only as a contraceptive device, 17.4% only as treatment for menorrhagia, and 33.2% for both indications. The vast majority of gynecologists (82.2%) reported a patient satisfaction rate of 70% or more. Among the gynecologists using the LNG-IUS as treatment for menorrhagia, the estimated overall patient satisfaction rate was more than 50%. Although most physicians expressed greater patient satisfaction with the LNG-IUS than with copper-releasing IUDs (p < 0.004), the majority of gynecologists still used the copper-releasing IUDs more frequently. Most considered the LNG-IUS as an appropriate method for endometrial protection in postmenopausal women using estrogen replacement therapy. CONCLUSIONS: Physicians should be made aware of the beneficial health effects of the LNG-IUS, particularly in premenopausal women with menorrhagia and for endometrial protection during hormone replacement.

Flexible starting schedule for oral contraception: effect on the incidence of breakthrough bleeding and compliance.

OBJECTIVE: To compare the effect of starting oral contraceptives on the first day of menses with the effect of starting on the day of menses' cessation (but no later than the 5th day following its onset), on the incidence of early breakthrough bleeding. METHOD: Oral contraceptives containing 30 micrograms ethinylestradiol and 75 micrograms gestodene were prescribed to 200 consecutive healthy women in whom oral contraceptives were found to be the most suitable method of contraception. In the first 100 women, treatment was started on the 1st day after the onset of menses (Day 1 group), and in the remainder, treatment was started on the day of menses' cessation, but no later than the 5th day following its onset (Flexible group). RESULTS: The Flexible group had better compliance and a reduced incidence of breakthrough bleeding. No differences were observed between the two groups for age, parity and gravity, or contraceptive failure. CONCLUSIONS: Oral contraceptives may be initiated on the day of menses' cessation, but no later than the 5th day following its onset. This regimen might increase patient compliance and lower the incidence of breakthrough bleeding, probably without adversely affecting contraceptive efficacy.

Prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist.

OBJECTIVE: To describe our experiment with the treatment of GnRH-a in premenarchal girls with idiopathic central precocious puberty (CPP). PATIENTS AND METHODS: Twenty-eight girls, aged 6.5-11 years, with idiopathic central precocious puberty were treated every 28 days with an intramuscular depot gonadotropin releasing hormone agonist (GnRH-a) in an attempt to delay sexual maturation. RESULTS: Eight of the 28 (28.5%) developed vaginal bleeding after GnRH-a administration. Of these, prolonged vaginal bleeding of 11-13 days occurred in four girls, three recurrent episodes occurred in one during the second injection, and in one other girl the 4th episode occurred after 6 months of treatment. CONCLUSION: Uterine bleeding following GnRH-a treatment in premenarchal girls with CPP is common, and may be massive and recurrent, since most episodes resolved spontaneously and necessitated no further treatment, careful advice should be given to the girls and their families prior to treatment initiation, in an attempt to avoid unnecessary anxiety and achieve better compliance.

A delayed starting schedule of oral contraception: the effect on the incidence of breakthrough bleeding and compliance in women.

OBJECTIVES: To assess the effect of oral contraception started on the first day of menses and the fifth day following its onset, on women's compliance and the incidence of early breakthrough bleeding. METHODS: Oral contraceptives (OCs) containing 30 micrograms ethinylestradiol and 75 micrograms gestodene were prescribed to 100 consecutive, healthy women for whom OCs were found to be the most suitable method of contraception. In the first 50 women, OCs were started on the first day of menses (day 1 group), while in the remaining 50 women, OCs were started on the fifth day after the onset of menses (day 5 group). RESULTS: The day 5 group had better compliance and a reduced incidence of breakthrough bleeding. No differences were observed between the two groups regarding age, parity and gravity. CONCLUSION: Starting an OC regimen should include initiation on the fifth day following the onset of menses. This regimen might increase patient compliance and lower the incidence of breakthrough bleeding.

Uterine activity after betamethasone administration for the enhancement of fetal lung maturation.

OBJECTIVE: To assess the effect of steroids administered for the enhancement of fetal lung maturation on uterine activity. DESIGN: A retrospective analysis. SETTING: High-risk Pregnancy Unit, Golda Medical Center, Petah Tikvah, Israel. PATIENTS: Fifty-nine courses of betamethasone therapy prescribed for various indications other than premature contractions were studied in 29 pregnant women at 26-34 weeks' gestation. MEASUREMENTS: Uterine activity was monitored on the day of the first (but prior to) beta-methasone injection, then daily for the next 3 consecutive days. The number of uterine contractions during the first 30 min of each tocodynamometric tracing was assessed. RESULTS: The frequency of uterine activity after steroid administration is significantly higher in multiple pregnancies as compared to singletons, and significantly increases as the duration of pregnancy increases. However, labor was not induced and all women delivered at least 1 week after the last betamethasone injection. CONCLUSIONS: Since the increased uterine activity after administration of steroids for the enhancement of fetal lung maturation does not provoke labor, it is suggested that this increase in uterine activity seems to act as a temporary phenomenon. Therefore conservative management, rather than tocolysis, would seem appropriate.

The value of hysteroscopic evaluation in patients with preclinical in-vitro fertilization abortions.

The study was conducted on 144 women who experienced preclinical abortions, i.e. a transitory rise in beta-human chorionic gonadotrophin (HCG) without any clinical or sonographic evidence of pregnancy, to identify the relationship between preclinical abortions and intrauterine pathology. Hysteroscopy was performed 1-2 weeks after the decline of beta-HCG concentrations to negative values. Intrauterine adhesions were detected in three patients (2.1%), most of these being of the mild type. Concomitant intrauterine abnormalities, mainly uterine septa, were found in 14 (9.7%) cases. We believe that preclinical abortions do not predispose intrauterine adhesions and curettage is superfluous. An incomplete uterine septum seems to be the major factor predisposing this early pregnancy wastage. Hysteroscopy following this condition is an easy and efficient means for both identifying intrauterine pathology and excluding adhesions.

Menstrual characteristics of women suffering from insulin-dependent diabetes mellitus.

OBJECTIVE: To assess the frequency of menarche and menstrual disturbances among women suffering from insulin-dependent diabetes mellitus, and to evaluate their correlation to the onset of diabetes, its duration, and complications. RESEARCH DESIGN AND METHODS: Retrospective analysis of the menstrual regularity and gynecologic and fertility history of 100 women suffering from insulin-dependent diabetes mellitus. These data were compared with information obtained from the patients' medical records regarding the age at onset of diabetes, its management, control, and complications. RESULTS: The average age at menarche was 13.5 years. Delayed menarche tended to appear in girls whose diabetes was diagnosed before the age of menarche, and before the age of 10 years. Menstrual disturbances, such as oligomenorrhea, amenorrhea, and polymenorrhea, occurred in 32% of the women. A significant correlation was found between late menarche and menstrual disturbances. Furthermore, patients with diabetic complications had a higher incidence of menstrual disorders compared with uncomplicated diabetic patients. CONCLUSIONS: It appears that women with insulin-dependent diabetes mellitus who had been diagnosed prior to menarche had a higher probability of delayed menarche, and were at higher risk for development of menstrual disturbances, including amenorrhea with subsequent fertility disorders.

Hyperprolactinemia after treatment of long-acting gonadotropin-releasing hormone analogue Decapeptyl in girls with central precocious puberty.

OBJECTIVE: To clarify the effects of prolonged treatment with long-acting GnRH analogue on serum PRL levels. DESIGN: Blood PRL levels were measured at 9 A.M. every 28 days for a period of 6 months. SETTING: Pediatric Endocrine Clinic, Hasharon Hospital, Petah Tiqva, Israel. PATIENTS: Thirteen girls with idiopathic central precocious puberty. RESULTS: Hyperprolactinemia developed in 5 of 13 girls after treatment with long-acting GnRH-a; mean blood PRL in all 13 girls rose significantly from 11.9 +/- 5.6 to 21.5 +/- 12.5 micrograms/L (mean +/- SD). CONCLUSIONS: The mechanism of hyperprolactinemia in our patients is unclear. It may have resulted from a decline in the release of the hypothalamic PRL inhibitory factor. Clinically, transient hyperprolactinemia during long-acting GnRH-a treatment for central precocious puberty also may reflect a constant depression of LH secretion.

Umbilical artery velocimetry in insulin dependent diabetes mellitus (IDDM) pregnancies.

Seven hundred and sixty seven Doppler umbilical artery velocity waveform analyses were performed in 108 pregnant insulin-dependent diabetes mellitus (IDDM) women. No significant correlation between mean third trimester systolic to diastolic (S/D) ratio and either mean blood glucose (r = 0.19) or glycosylated hemoglobin levels (r = 0.28) was found. Mean second and third trimester S/D ratios differed significantly in patients with or without vascular disease (P less than 0.05). Furthermore, women without vasculopathy who demonstrated an elevated S/D developed preeclampsia and delivered appropriate for gestational age infants while patients with vascular disease or chronic hypertension and elevated third trimester S/D (greater than 3) delivered intra uterine growth retarded (IUGR) infants. Moreover, in most of the latter group elevated S/D ratios were recorded in the second trimester prior to ultrasound documentation of IUGR. Our data suggest that in the absence of vasculopathy normal fetal placental resistance can be expected in most pregnancies complicated by diabetes. Patients with vasculopathy are at higher risk for fetal IUGR, which may be identified by early umbilical artery velocimetry.

The value of GnRH agonists in the treatment of failed cycles in an IVF-ET program: a comparative study.

Occasionally, menotropins fail to induce ovulation for IVF-ET, due to early luteinization resulting in high cancellation rates of 15-40% of cycles. The efficacy of GnRH agonists in reducing these problems was prospectively studied in 91 women undergoing repeated IVF-ET, after desensitization with GnRH agonists. In all patients, the cycles that had been induced by menotropins alone failed due to early luteinization. By comparing these patients to a control group with significantly lower cancellation rates as well as significantly higher fertilization, the cleavage and pregnancy rates were achieved for the former group (p less than 0.001 in all parameters). Pituitary down-regulation by means of GnRH agonists prior to the induction of ovulation seems to be an effective and rewarding method for minimizing cancellation rates, and for achieving improved results in IVF-ET therapy.

The vaginal contraceptive diaphragm and the condom--a reevaluation and comparison of two barrier methods with the rhythm method.

The use-effectiveness and continuation rates of two barrier methods of contraception, the diaphragm and condom, were studied during a two-year follow-up in a group of 85 and 98 women, respectively. All were highly motivated. Results were compared to a group of 64 women using the periodic abstinence or rhythm method, i.e. not using any contraceptive. The patients selected the method of contraception they preferred and were instructed in their proper use. Results showed good continuation rates in the groups using a diaphragm and the condom for 2 years, for a total follow-up of 5570 cycles. Pregnancy rate after 24 months of use, as calculated by Pearl's formula, was 2.48 for the diaphragm, 3.21 for the condom, and 5.19 in the rhythm group. No serious side effects or complications occurred in either group. The study demonstrated a fair acceptability and use-effectiveness for barrier contraceptive. We suggest that these harmless and complication-free methods may still be reasonable alternatives for the "modern" methods, the pill and the IUD.

The value of GnRH analogue therapy in IVF in women with unexplained infertility.

Seventy-six women with unexplained infertility, undergoing in-vitro fertilization and embryo transfer (IVF-embryo transfer), were selected for three different ovulation induction protocols. In group I, induction of ovulation was performed with pure follicle-stimulating hormone/human menopausal gonadotrophin/human chorionic gonadotrophin (pFSH/HMG/HCG). Group II patients were given a combined therapy consisting of a gonadotrophin-releasing hormone (GnRH) analogue, decapeptyl (DTRP6) followed by pFSH/HMG/HCG. In group III, patients underwent two IVF-embryo transfer cycles, serving as their own controls. The initial cycle was induced with pFSH/HMG/HCG while the second was stimulated using decapeptyl/pFSH/HMG/HCG. Significantly higher rates of fertilization, cleavage and pregnancy (P less than 0.001, P less than 0.07, P less than 0.001, respectively) were achieved in group II patients to whom combined GnRH agonists and gonadotrophins were given. Furthermore, among group III patients, no pregnancies occurred during the initial IVF-embryo transfer cycles whereas a 23% pregnancy rate (P less than 0.001) was obtained after GnRH agonist therapy. Our results indicate that the combination of GnRH agonists and gonadotrophins is of value in cases of unexplained infertility. Further, larger studies must be performed before the true efficacy of this mode of therapy can be determined in women with unexplained infertility.

IVF-ET in women with refractory polycystic ovarian disease.

Polycystic ovarian disease may be a cause of hormonal infertility. This condition is often refractory to therapy. Three groups of randomly chosen women with refractory polycystic ovarian disease (PCOD) were treated by induction of ovulation with pFSH/hCG, pFSH/hMG/hCG or after down-regulation of the ovaries with a GnRH analogue (Decapeptyl). Out of 18 patients six conceived in the first in vitro fertilization-embryo transfer (IVF-ET) cycle, and two further women conceived in a later cycle. It is suggested that patients with refractory PCOD should be referred for IVF-ET therapy, possibly after treatment with a GnRH analogue.

Ovarian cyst formation: a complication of gonadotropin-releasing hormone agonist therapy.

Since gonadotropin-releasing hormone (GnRH) analogs were introduced into clinical therapeutic use, several side effects directly related to the hypoestrogenic state have been reported. The authors have encountered a rather infrequent complication, namely ovarian cystic formations, when using these compounds for selected in vitro fertilization and embryo transfer (IVF-ET) cases. In 7 of 24 patients with Decapeptyl (D-Trp6-luteinizing hormone-releasing hormone [LH-RH], Ferring, Kiel, FRG) treatment, and in 5 of 22 patients treated with Buserelin (Superfact, Hoechst A.G., Frankfurt, FRG), solitary ovarian cysts developed during the down-regulation phase. Their growth did not change during ovulation induction with menotropins. Although the mechanism of ovarian cyst formation during GnRH agonist treatment is not clear, their presence does not appear to interfere with the fertility of these women.

The vanishing fetus. A report of 17 cases of triplets and quadruplets.

The incidence of multiple conceptions is higher than the incidence of multiple deliveries. The "vanishing fetus" is a relatively new concept being a direct result of the advent of ultrasonography. Early first trimester loss of one or more conceptuses accounts for this phenomenon. The patient may be symptomatic (bleeding, pain, abdominal cramps) but in most instances, the finding is fortuitous. We report 17 cases of a vanishing fetus in a multiple gestation of greater than twins. In 13 patients one fetus vanished in the course of pregnancy while in four cases two fetuses disappeared from each gestation. The phenomenon was observed up to the 16th week of pregnancy. It is our feeling that the finding of a vanishing fetus should be recorded early, as the prognosis for pregnancy bleeding is different than in the singleton pregnancy. Thus information regarding this phenomenon should be given to couples who consider artificial reduction of fetuses in the multiple gestation.

Ovarian cyst aspiration during in vitro fertilization/embryo transfer (IVF/ET) cycles.

Fifteen patients treated in an IVF program with ovarian cysts were retrospectively evaluated. Ten women with ovarian cysts formed during induction of ovulation were treated by puncture and aspiration and compared to a control group of five patients in whom the ovarian cysts could not be punctured. Induction protocols in both groups were based on hMG/hCG or pFSH/hCG administration. In patients in the study group the mean volume aspirated from cysts was 7.4 +/- 2.1 ml. Mean estrogene (E2) levels on the day of hCG were 1411 +/- 213 and 1036 +/- 177 pg/ml in the hMG and pFSH groups, respectively. Mean progesterone (p) levels were 1.6 +/- 0.4 and 1.9 +/- 0.3 ng/ml, respectively. Oocyte collection was done with the aid of a vaginal ultrasound transducer. A mean of 6.2 and 5 oocytes was picked up respectively, with a fertilization rate of 74.3 and 69.1%. In all cases embryo transfer was performed. Two clinical pregnancies were achieved, one in each of the induction protocol groups. In the control group, patients underwent early luteinization, i.e., requiring cancelation of the cycle, after the ovarian cysts had not been aspirated. It is suggested that puncture and aspiration of ovarian cysts occurring during induction of ovulation may be an efficient method to avoid early luteinization. It should be evaluated further.

Fetal surveillance in insulin-dependent diabetic pregnancy: predictive value of the biophysical profile.

Ninety-eight insulin-dependent diabetic pregnancies underwent monitoring by means of 978 biophysical profiles from 28 weeks' gestation until parturition. Only 2.9% of the 978 tests had abnormal results (score less than or equal to 7). When performed within 2 days before birth, a normal biophysical profile predicted the 1-minute Apgar score to be normal in 92% and 5-minute Apgar score in 99%. When all biophysical profiles ever performed were included, the predictive value improved to 100%. The baby's first cry within 1 minute after birth was predicted in 95%. Furthermore, the predictive value of a normal biophysical profile regarding the absence of ominous intrapartum cardiotocographic patterns was excellent (95%). The specificity was in general good (80% to 90%), but the predictive value of abnormal test results and sensitivity were almost without exception poor. It seems that the very low rate of abnormal biophysical profiles indicates that obstetric interventions were made immediately after the occurrence of the first sign of fetal jeopardy; thus improved results were obtained.

Comparison of a fixed and dynamic protocol for embryo replacement in an IVF/ET programme.

Implantation after embryo transfer is considered a major obstacle in terms of pregnancy rates after in-vitro fertilization. A flexible approach to the date of replacement, based on the fact that the most suitable embryonic structure for proper implantation is the four- to eight-cell embryo, has been studied. One-hundred-and-twenty patients with various aetiologies of infertility were stimulated with HMG or combined HMG and FSH, then treated by three different methods of embryo replacement. In group I embryos were replaced in mothers 48 h after ovum retrieval; in group II replacements were carried out 72 h after retrieval; and in group III replacements were related to embryonic cleavage development. Mean levels of oestradiol when HCG was given averaged 1301 +/- 121 pg/ml, 1016 +/- 96 pg/ml and 1182 +/- 101 pg/ml in the three groups, respectively. There was no significant difference in the average number of embryos transferred among the various groups. The pregnancy rates per transfer were 21.8, 24.2 and 38.7%, respectively (P less than 0.001). Although more investigation is required, a dynamic approach to embryo replacement might significantly improve pregnancy rates, because of improved interactions between the embryos and the uterus.