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Sonohysterography or sonographic uterine cavity visualization by uterine cavity distension may help in distinguishing true endometrial thickening from other intracavitary pathologic conditions assuming the same appearance on conventional sonography. We examined 15 women with thickened endometrium (range 10-25 mm) on sonography performed for postmenopausal bleeding. Subsequent sonohysterography with saline revealed a polypoid structure in seven women, a normal uterine cavity in four, and thickened endometrium in four. All patients underwent hysteroscopic evaluation of the uterine cavity. Hysteroscopy confirmed the sonohysterographic findings in 14 patients (93.3%). Hysteroscopic resection of the polypoid structures was performed while the remaining patients underwent diagnostic curettage. Histologic examination of the seven polypoid structures revealed benign endometrial polyp in six and one pedunculated submucous fibroid. In patients undergoing diagnostic curettage, histologic examination revealed three cases of glandular hyperplasia, one case of cystic (atrophic) hyperplasia, one case of papillary endometrial adenocarcinoma, and two cases were inadequate for diagnosis. The advantage of sonohysterography in distinguishing endometrial thickening from intracavitary polyp or fibroid is clearly demonstrated. This technique can help in tailoring the correct treatment in various conditions presenting as postmenopausal bleeding.

Objective: To examine the IVF-ET outcome of couples with unexplained infertility treated by husband versus donor sperm., Design: A retrospective analysis of the IVF-ET outcome of couples with unexplained infertility treated by either husband or donor sperm and in a subgroup of patients treated simultaneously by husband and donor sperm., Setting: IVF Unit, Serlin Maternity Hospital, Tel Aviv, Israel., Patients: Couples diagnosed as having unexplained infertility underwent IVF at our Unit; included were 96 couples treated by husband insemination (group A), 27 couples who received donor insemination because of azoospermia (group B), and 8 couples who sought donor insemination after having previously failed IVF (group C)., Results: No statistically significant difference was found between groups A and B regarding age of the females, duration of infertility, number of IVF cycles, fertilization rate, number of ETs, and pregnancy rate. Oocytes collected in group C were subdivided further into two groups: 45 were incubated with husband sperm and 46 were incubated with donor sperm. Fertilization rates were 46.6% and 50%, respectively. One pregnancy occurred., Conclusion: In couples with unexplained infertility who had undergone IVF-ET with husband insemination, the fertilization and pregnancy rates were similar to those of couples who were treated by donor sperm.

Sonohysterography, or sonographic uterine cavity visualization by uterine cavity distension, may help to distinguish true endometrial thickening from other intracavitary pathological conditions, assuming the same sonographic appearance. We examined 1.5 women with a thickened endometrium (range 10-25 mm) in sonography performed for postmenopausal bleeding. Sonohysterography revealed a polypoid structure in seven women, a normal uterine cavity in four women, and a thickened endometrium in four women. All the women underwent hysteroscopic evaluation of the uterine cavity. Hysteroscopy confirmed the sonohysterographic findings in 14 women (93.3%). Hysteroscopic resection of the polypoid structure was performed while the other patients underwent diagnostic curettage. Histological examination of the seven polypoid structures revealed benign endometrial polyps in six patients, and one pedunculated submucous fibroid. In the patients undergoing diagnostic curettage, histological examination revealed three cases of glandular hyperplasia, one of cystic (atrophic) hyperplasia, and one of papillary endometrial adenocarcinoma. Two cases were inadequate for diagnosis. The advantage of sonohysterography in distinguishing endometrial thickening from intracavitary polyps or fibroids was clearly demonstrated. This technique can help in tailoring the correct treatment in various conditions presenting as postmenopausal bleeding., (Copyright 1994 International Society of Ultrasound in Obstetrics and Gynecology)

The fourth to eighth in-vitro fertilization cycles of patients who had previously reached the stage of embryo transfer without conceiving were evaluated. A total of 426 cycles were received in women ranging in age from 25 to 46 years. The patients underwent from four (169 women) to eight (27 women) treatment cycles, using four established protocols for induction of ovulation. There was no statistical difference in the age, aetiology, duration of infertility and distribution of the various protocols among the analysed groups. The pregnancy rates in cycles 4-8 were 19.5, 15.4, 10.8, 16.7 and 11.8% respectively (mean 16.2% per cycle) and were not statistically different. There was no trend of reduced success when the number of attempts increased. The overall live birth rate was 12.4%. The pregnancy rate was comparable between age groups. No protocol proved to be significantly superior to others when pregnancy rate per embryo transfer was assessed. We concluded that the pregnancy rate in cycles 4-8 was stable, including those of patients up to 42 years of age. Continuous efforts are therefore advised for at least up to this age and number of attempts. A change of an induction protocol in subsequent cycles, after repeated failure, is not statistically justified.

The possible antiestrogenic effect of clomiphene citrate on endometrial growth was assessed by serial transabdominal ultrasonographic measurements in 46 women with unexplained infertility. A significantly higher (p < 0.05) rate of endometrial growth was observed in the 8 women who conceived compared with the 38 women who failed to conceive. A thicker endometrium (4.6 +/- 0.3 mm) was observed from the third day before ovulation as well as a higher average growth rate in the three days prior to ovulation (0.7 +/- 0.1 mm/day) in the group that achieved pregnancy compared to a lower endometrium (2.1 +/- 0.2 mm) from the third day before ovulation and a slower growth rate in the three days prior to ovulation (0.2 +/- 0.0 mm/day) in the group that did not achieve pregnancy (p < 0.05). These data suggest that clomiphene citrate may exert an antiestrogenic effect on the endometrium, and thus interfere with implantation.

One hundred and thirteen cases of polyhydramnios diagnosed by repeated ultrasonic examinations in singleton pregnancies were divided into two groups according to the trend of change in the amniotic fluid volume between the first and the second ultrasonic examination. Group A patients (65 cases) showed an increase or no change in amniotic fluid volume, and in group B (48 cases) a reduction in amniotic fluid volume to mild polyhydramnios or to normal amniotic fluid volume was observed. A significantly increased rate (p < 0.05) of maternal complications such as diabetes mellitus, pregnancy-induced hypertension, urinary tract infections, premature rupture of membranes and premature delivery was observed in group A. More abdominal deliveries and an increased rate of fetal anomalies, fetal abnormal presentations, intrauterine fetal death and neonatal death also occurred in this group. Group B patients, most of whom were idiopathic, showed a very favorable outcome.

In a retrospective study we evaluated 4 controlled ovarian hyperstimulation (COH) protocols for in vitro fertilization (IVF) treatment. Treatment cycles 4 through 8 were analyzed in patients, who in 3 previous attempts reached the stage of embryo transfer (ET) but did not conceive. The 426 recorded cycles included all indications for IVF, but not the male factor. The age range was 25-46 years. Patients underwent from 4 cycles (169 women) to 8 cycles (27 women). The COH protocols used included established combinations of menotropins, clomiphene citrate/hMG, and short and long protocols of GnRH analogs followed by hMG. There were no statistically significant differences in patient age, etiology and duration of infertility, or distribution of the various COH protocols among the groups of patients. No single protocol was significantly superior to any other when the pregnancy rate per cycle was assessed. The results did not justify changing a COH protocol which had lead to ET but not to pregnancy, for another protocol.

A retrospective analysis of ovarian hyperstimulation syndrome in high responders undergoing in-vitro fertilization (IVF) is presented. High responders were defined as having > 20 follicles and serum oestradiol > 3000 pg/ml after treatment with human menopausal gonadotrophin. Of the initial 30 IVF cycles in high responders, 23 developed a moderate-to-severe ovarian hyperstimulation syndrome (76.7%). Subsequently, 15 other IVF cycles in high responders were combined with a repeated aspiration of ovarian follicles and corpus luteum cysts just prior to embryo transfer. Only three patients (20%) developed a moderate ovarian hyperstimulation syndrome (P = 0.0004). We conclude that repeated follicular aspiration is safe and results in a significant reduction in the incidence and severity of this condition in high responders undergoing IVF.

Objective: To assess the effect of age and ovarian function on endometrial receptivity., Design: Retrospective comparison between standard IVF and ovum donation in younger and older patients (< 40 and > or = 40 years of age, respectively)., Patients: In standard IVF, there were 325 transfer cycles in older patients and 1,103 transfer cycles in younger ones. In ovum donation, there were 236 transfer cycles in older patients and 222 cycles in younger women. Ovum recipients were then redivided into two groups, according to ovarian function: ovarian failure group (219 cycles) and eugonadal group (239 cycles) in patients with retained ovarian function as manifested by regular menstrual cycles and normal gonadotropins., Results: In standard IVF, clinical pregnancy rates (PRs) were significantly lower in older patients (12.9% versus 23.8%, respectively). In ovum donation, clinical PRs were also significantly lower in older patients (21.2% versus 29.3%, respectively). A significantly higher clinical PR (31.1%) was noted in patients with ovarian failure, compared with both eugonadal patients undergoing ovum donation (19.7%) and standard IVF patients (21.3%)., Conclusions: The decrease in endometrial receptivity with age is responsible for the higher rate of implantation failure in older women. Patients with nonfunctioning ovaries do better than eugonadal patients in ovum donation programs.

During a 5.5 year period, 309 clinical pregnancies were recorded in our in-vitro fertilization (IVF) unit. A single gestational sac was identified by early ultrasonography in 233 patients, while in 76 others, multiple gestational sacs were noted. 'Take-home baby' rate, in patients in whom multiple sacs were observed, was higher than that in patients with a single sac. Delivery of at least one live newborn occurred in only 73.8% of patients with a single sac, compared with 93.3% and 91.7% in patients with two and three gestational sacs, respectively. Conversely, the early and late abortion rates were decreased in patients with multiple sacs. Embryonic implantation rate, defined as the ratio of gestational sacs observed to the number of embryos transferred, was found to be a valuable prognostic factor for a live delivery, and can serve as a tool in assaying the prognosis of pregnancy detected by early sonography. The observation of a higher 'take-home baby' rate in cases with multiple sacs identified by ultrasound and with higher embryonic implantation rate, might be the result of a better embryo quality and/or improved uterine receptivity, promoted by a favourable hormonal milieu or by as yet unknown endometrial factors.

A total of 30 patients with multifetal pregnancies, all resulting from treatment with superovulatory agents or assisted reproductive techniques, underwent embryo reduction. All patients had three or more fetuses (one sextuplet, two quintuplets, seven quadruplets and 20 triplets). The procedure was carried out using intra-embryonal injection of 0.9% sodium chloride solution. Embryo reduction was carried out via the transabdominal approach in 10 patients, performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other patients, at 8-10 weeks of gestation. In the transabdominal group, one patient aborted following repeated attempts at embryo reduction while the other nine gave birth to healthy newborns (eight twins and one triplet). In the transvaginal group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation), 14 pregnancies resulted in a delivery of at least one live newborn (13 twins and one singleton), one patient had a late abortion at 24 weeks' gestation and another was delivered at 27 weeks' gestation due to severe pre-eclampsia. Transvaginal ultrasound-guided needle procedures are commonly practised in most in-vitro fertilization units. The employment of this route for embryo reduction, performed at an earlier gestational age and with the use of a non-toxic substance such as 0.9% saline solution, is advocated.

Animal and human research has indicated the presence of receptors to luteinizing hormone-releasing hormone (LH-RH) in the ovaries. However, the role of these receptors is not yet clear. Forty-five patients were treated with Suprefact (D-Serg-Des-Gly10-GnRGH), starting in the midluteal phase of a nonstimulatory menstrual cycle. The Suprefact (300 micrograms t.i.d.) was administered as a nasal spray until the administration of human chorionic gonadotropin (hCG). On the third to fifth day of the following menstrual cycle, the patients were treated with a high dose of human menopausal gonadotropin (hMG). hCG was administered when at least two follicles reached a mean diameter of 18 mm. Five of these patients who ovulated spontaneously and had normal menstrual cycles did not respond to the stimulation with hMG. Treatment was stopped after 12 days of hMG administration. During the following cycle of the five patients, levels of gonadotropins were found to be in the normal range, and all of them responded as expected to hMG administered for 3 days only (hMG test). These findings suggest that LH-RH agonist may interfere with ovarian steroidogenesis.

Objective: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation., Setting: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital., Patients: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit., Interventions: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach., Results: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours., Conclusion: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle.

The efficiency of cryopreserved donor semen versus fresh donor semen in an in vitro fertilization/embryo transfer programme was evaluated. Thirty-nine in vitro fertilization/embryo transfer cycles were performed using fresh donor semen (group A) and 74 cycles were carried out using cryopreserved semen (group B). All patients underwent a uniform controlled ovarian hyperstimulation using high doses of human menopausal gonadotropins. Oocytes were retrieved transvaginally under ultrasound imaging. Semen (fresh or frozen-thawed) were prepared for insemination by a washing technique. Each ovum was inseminated with 500,000-600,000 motile spermatozoa. No significant difference was noted between the two groups regarding female age, duration of infertility, and number of ova retrieved per aspiration. Even though the fertilization rate in group B was significantly lower than in group A (55.5 +/- 3.8 vs 70.4 +/- 3.5, P = 0.008), pregnancy rates per embryo transfer were similar--39.3 and 38.5%, respectively.

Most ovum donation (OD) programs involve cycle synchronization between recipient and donor for normally cycling recipients and a complex estrogen-progesterone replacement regimen for recipients with ovarian failure. In 1987, Serhal and Craft (1) suggested the use of a fixed-dose estrogen-progesterone regimen for recipients who were normally ovulatory and to those with ovarian failure. Following this protocol, and simplifying it still, the authors administered 6 mg estradiol valerate (E2) daily orally starting on day 2-6 of induced withdrawal bleeding, augmented with 100 mg progesterone in ethyl oleate (P) intramuscularly daily, starting any time between 4 days prior to and the day of oocyte pickup. All recipients underwent embryo transfer at a 2-pronuclei (2PN)-10-cell stage. A group of 21 patients underwent 26 treatment cycles, resulting in 16 pregnancies. Twelve of the patients gave birth, one to triplets, two to twins, and nine to singletons. Four patients miscarried in the first trimester of pregnancy.

A randomized, prospective blind study was carried out to investigate the need for luteal phase support in patients undergoing in-vitro fertilization (IVF). One-hundred-and-fifty-six patients undergoing IVF in cycles stimulated with human menopausal gonadotropin (HMG) and human chorionic gonadotrophin (HCG) stimulated IVF, were divided into three different groups for luteal phase treatment. Fifty-four patients received dydrogesterone three times daily (TID) beginning on the day of embryo transfer (ET). Fifty-one patients received HCG on days 3, 6 and 10 following ET. Fifty-one patients received placebo p.o. TID beginning on the day of ET. There was no difference between the groups in pregnancy rate, rate of spontaneous abortion, proportion of normally developing fetuses or rate of chemical pregnancy. The data indicate that supplementation of the luteal phase may not improve the success rates of IVF-ET cycles.

The term "unexplained infertility" is applied to a couple in whom after an elaborate workup no apparent reason for infertility is found. Between August 1985 and May 1987, 435 patients underwent 720 treatment cycles in an in vitro fertilization-embryo transfer (IVF-ET) unit. Eighty-three of the patients had unexplained infertility as their indication for IVF-ET. Fifty-two (group A) had primary unexplained infertility and 31 (group B) had secondary unexplained infertility. Group A underwent 87 and group B underwent 50 treatment cycles. Forty-six ET were performed in group A and 34 in group B. Clinical pregnancies were achieved in 20 patients of group A (11.5% per treatment cycle) and 13 of group B (26.0%), for a combined rate of 16.8% per cycle. Patients with tubal infertility treated in the program had a pregnancy rate of 18.8% per treatment cycle. The performance of the secondary unexplained infertility group is significantly better than that of the primary unexplained infertility group. However, the overall results with patients with unexplained infertility are similar to those patients treated for tubal infertility.

A simple, rapid, and sensitive solid-phase immunoassay procedure for the determination of estrone-3-glucuronide (E1-3-G), which uses chemiluminescence as the end point in unextracted morning urine, is described. Thirty-one patients undergoing induction of ovulation in an in vitro fertilization (IVF) unit participated in the study. From day 3 of the menstrual cycle until the day of hCG administration, morning blood samples and morning urine specimens were collected for the determination of serum 17 beta-estradiol (E2) and urine E1-3-G, respectively. A good correlation was noted between E2 measured by radioimmunoassay (RIA) and the E1-3-G measured by chemiluminescence immunoassay (CIA), from day 5 up to the day of hCG administration (0.6 less than r less than 0.85, P less than 0.001). It is evident from this study that the CIA measurement of E1-3-G in morning urine is an accurate and rapid (2.5 hours) method and is convenient for monitoring induction of ovulation with human menopausal gonadotropins.

Until recently most of the current in vitro fertilization and embryo transfer (IVF-ET) programs used laparoscopy for oocyte retrieval and included hospitalization in the treatment. The establishment of a successful ambulatory IVF program that uses ultrasonically guided oocyte aspiration, is described. Between August 1985 and February 1987, 384 percutaneous transvesical ultrasonically and transvaginally guided follicle aspirations were performed on 414 patients, following ovarian stimulation with hMG and hCG. Ninety two clinical pregnancies were confirmed by ultrasound. The clinical pregnancy rate was 26.8% when based on the number of embryo transfers. There were 16 multiple pregnancies (17.4%), 18 miscarriages (19.5%), and two tubal pregnancies (2.1%). The most important factors contributing toward the success of this program were rigid adherence to clinical and laboratory protocols, and the maintenance of a strict quality control. The ambulatory management was very well accepted by the patients, who during the entire period of ovarian stimulation had minimal disruption of their routine activities.