Yael Gonen

Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF)

The texture and the thickness of the endometrium as assessed by transvaginal sonography were prospectively evaluated in 123 patients undergoing IVF treatment. Three different types of endometrial patterns could be distinguished: (A) an entirely homogeneous, hyperechogenic endometrium; (B) an intermediate type characterized by the same reflectivity of ultrasound as the myometrium, with a nonprominent or absent central echogenic line; and (C) a multilayered endometrium consisting of prominent outer and midline hyperechogenic lines and inner hypoechogenic regions. On the day before oocyte retrieval, endometrial thickness was significantly greater in the group of patients who achieved pregnancy than in the group who did not (8.7±0.4 vs 7.5±0.2 mm, respectively; P<0.01) and significantly more patients had multilayered, pattern C, endometrium (75% in pregnant women vs 42.4% in nonpregnant women; P<0.01). No pregnancy occurred when the endometrial thickness was less than 6 mm. When type C endometrium >-6 mm thick was seen, the pregnancy rate per embryo transfer was 39%. When type A or B endometrial pattern was seen, the negative predictive value for the occurrence of pregnancy was 90.5%. Our results suggest that transvaginal sonographic evaluation of endometrial texture and thickness may be an indicator of the likelihood of achieving pregnancy.

Endometrial thickness and growth during ovarian stimulation: a possible predictor of implantation in in vitro fertilization

The present study was undertaken to evaluate endometrial thickness and the amount of endometrial growth (delta) in patients who conceived during in vitro fertilization (IVF) (n = 36) compared with matched women who did not conceive (n = 72). Estradiol (E2) and endometrial thickness were measured daily from cycle day 10 to the day after human chorionic gonadotropin (hCG). Mean endometrial thickness and E2 levels on cycle day 10 did not differ. On the day before ovum retrieval, significantly thicker endometrium was observed in the pregnant than in the nonpregnant women (8.6 +/- 0.3 [SEM] and 7.1 +/- 0.3 mm, respectively; P less than 0.0005), whereas the mean E2 levels did not differ. The delta endometrial growth was greater in the women who conceived than in the nonpregnant group (4.3 +/- 0.2 and 2.5 +/- 0.2 mm, respectively; P less than 0.0005). The fertilization rate and serum E2 levels did not correlate with endometrial thickness nor with delta endometrial growth. Our data suggest that the amount of endometrial growth during ovarian hyperstimulation and the endometrial thickness on the day before oocyte retrieval deserve further study as possible predictive parameters for implantation.

Gonadotropin suppression with oral contraceptives before in vitro fertilization.

One hundred eighty-one stimulation cycles in which gonadotropin suppression with oral contraceptives (OCs) preceded induction of follicle stimulation (study group) and 113 stimulation cycles without pituitary suppression (control group) were compared. The mean length of ovarian suppression was 35.3 +/- 0.9 days. No spontaneous luteinizing hormone (LH) surges occurred when the use of OC preceded ovarian hyperstimulation, whereas in the control group the incidence of LH surges was 19.5%. The mean amount of human menopausal gonadotropin required was significantly lower in the study group than in the control group (8.9 +/- 0.4 and 10.9 +/- 0.4 ampules, respectively). Significantly more follicles greater than or equal to 1.5 cm in diameter were seen on the day before oocyte retrieval and significantly more oocytes were retrieved per attempt in the group with OC pretreatment. Our data clearly demonstrate that OCs are useful in vitro fertilization stimulation protocols to facilitate scheduling of cycles and to prevent spontaneous LH surges.

Pregnancy and birth after transfer of embryos that developed from single- nucleated zygotes obtained by injection of round spermatids into oocytes

OBJECTIVE To use injection of spermatids into oocytes as a mode of infertility treatment in cases in which spermatozoa are not available. DESIGN Prospective clinical evaluation and case report. SETTING In Vitro Fertilization Unit, Herzliya Medical Centers, Herzliya-on-Sea, Israel. PATIENT(S) Thirteen couples with male factor infertility in which the male partner lacked spermatozoa in the ejaculate or testicular biopsy samples. INTERVENTION(S) Round spermatid injection and elongated spermatid injection into oocytes. MAIN OUTCOME MEASURE(S) Evaluation of the rate of two-pronucleated and single-nucleated zygote development. RESULT(S) The rate of two-pronucleated zygote development after round spermatid injection and elongated spermatid injection was relatively low (27% and 36%, respectively). Single-nucleated zygotes develop more frequently after round spermatid injection and elongated spermatid injection (35% and 17%, respectively) than after intracytoplasmic sperm injection with mature spermatozoa. A normal pregnancy and childbirth resulted from the transfer of 4 cleaving embryos, each of which developed from a single-nucleated zygote in a round spermatid injection treatment cycle with ejaculated spermatids. CONCLUSION(S) Embryos derived from single-nucleated zygotes after spermatid conception can be viable and give rise to an ongoing clinical pregnancy and childbirth.

A simplified coculture system with luteinized granulosa cells improves embryo quality and implantation rates: a controlled study.

OBJECTIVE To investigate the use of a simplified short-term coculture system with luteinized granulosa cells (GCs) in patients with failed IVF-ET. DESIGN Controlled clinical study. SETTING IVF unit, Department of Obstetrics and Gynecology, Carmel Medical Center. PATIENT(S) Patients with poor embryo quality in their previous IVF-ET cycles. INTERVENTION(S) Embryos from 40 patients, in which > 50% of the embryos were classified as poor quality in their previous IVF attempts, were grown on autologue GC culture system for a short period (24-48 hours) before being replaced in the uterine cavity. MAIN OUTCOME MEASURE(S) Embryo quality. RESULT(S) Significant decrease in poor quality embryos and increase in the proportion of good quality embryos were observed using a coculture system with autologue human GCs. Pregnancy rates in this groups of patients reached our standard IVF results during the same period. CONCLUSION(S) This study describes a simplified short-term coculture system with human autologue GCs. Poor quality embryos may be rescued to cleave regularly.

The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a;decapeptyl) and gonadotropins versus short-acting GnRH-a (buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF)

The efficiency of two ovarian stimulation protocols using different gonadotropin-releasing hormone agonists (GnRH-a) for in vitro fertilization (IVF) was examined and compared with human menopausal gonadotropin (hMG)-only stimulation. Fifty-four patients who had 57 aspiration cycles were treated with protocol 1, which consisted of long-acting GnRH-a D-Trp6 (Decapeptyl Depot) and hMG. Protocol 2 entailed intranasal administration of short-acting GnRH-a (Buserelin) and human menopausal gonadotropin (hMG) in 66 women, who underwent 70 aspiration cycles. Fifty-five patients who had 59 ovum pickups (OPU) treated with hMG only served as a control. No differences were observed in cycle parameters and hormonal concentrations among the three groups. The total clinical pregnancy rates per OPU for patients receiving protocols 1 and 2 were 12.3 and 27.1%, respectively (P<0.05). The pregnancy loss was significantly lower in protocol 2 than in protocol 1 (26.3 versus 71.4%;P<0.05). Our data show superiority of short-acting GnRH-a over the long-acting agents in achievement of pregnancy and its outcome, though neither was significantly different from the hMG-only protocol.

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.

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.

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.

Does transient hyperprolactinemia during ovarian hyperstimulation interfere with conception or pregnancy outcome

The significance of transiently increased serum prolactin (PRL) levels on pregnancy rates in in vitro fertilization (IVF) is unknown. The aim of this study was to evaluate PRL levels in IVF patients who conceived and in matched controls who did not. Thirty-seven IVF cycles resulting in pregnancy and 74 nonpregnant cycles were compared. Prolactin was measured before ovarian stimulation with clomiphene citrate, and human menopausal gonadotropin and estradiol (E2) and PRL were measured 8 hours after human chorionic gonadotropin (hCG) administration at midcycle. Before ovarian stimulation, serum PRL levels were not different in the pregnant and nonpregnant women (11.1 +/- 0.6 [mean +/- standard error] micrograms/l and 10.1 +/- 0.4 micrograms/l, respectively). After hCG, PRL levels were significantly higher in the pregnant women than in the nonpregnant women (20.8 +/- 1.6 and 16.0 +/- 0.9 micrograms/l, respectively; P less than 0.005) and more pregnant than nonpregnant women had elevated PRL levels (49% versus 28%, respectively; P less than 0.05). There was no correlation between PRL and E2 in either group. The abortion rate was not different between the women with elevated PRL (22.2%) and the normoprolactinemic women (31.6%). These results do not support treatment of transient hyperprolactinemia with dopamine agonists in IVF patients.