Isaac Ben-Nun

Relationship between embryo morphology and implantation rate after in vitro fertilization treatment in conception cycles

OBJECTIVE To investigate the relationship between the embryo number and morphology in conception cycles and the incidence of multiple pregnancies. DESIGN The study is based on information received from a computerized data base. SETTING In Vitro Fertilization Unit, Sapir Medical Center, Kfar Saba, Israel. PATIENTS A total of 117 consecutive pregnancies resulted from replacement of fresh embryos in our IVF-ET program. MAIN OUTCOME MEASURES The impact of embryo quality, as assessed by morphological parameters, on the multiple pregnancy rate (PR). RESULTS Implantation rates positively correlated with the number and the quality of transferred embryos. However, no multiple pregnancies occurred when only two embryos were replaced. There were no multiple pregnancies when only embryos of low quality (grades 1 and 2) were transferred. Furthermore, there was no correlation between the number of replaced embryos of poor quality and the rate of implantation. The multiple PR increased from 10% when a mixture of high and low quality embryos were transferred to 30.76% when only embryos of highest quality were transferred. CONCLUSION The implantation rate of transferred embryos is directly correlated with the morphological scoring. The results of the study suggest that the number of embryos transferred should be balanced against their morphological quality to reduce the rate of multiple pregnancies.

The impact of different types of anesthesia on in vitro fertilization-embryo transfer treatment outcome

ObjectiveOur objective was to evaluate retrospectively the influence of different types of anesthesia on the outcome of ovum retrieval.MethodsSedation combined with local anesthesia was used on 120 occasions (Group I), epidural block in 139 ovum retrievals (Group II), and general anesthesia in 173 cycles (Group III).ResultsNo differences were found in embryo yield or number or the quality of the embryos transferred. Of 99 pregnancies achieved, 66 live deliveries were recorded. Significantly lower clinical pregnancy rates were found in Group III (14.5%) compared with Group II (23.7%; P= 0.018) or Group I (25.8%; P=0.0074). Highly significant differences were found in the delivery rates between Group HI (8.7%), Group II (20.11%; P=0.0017), and Group I (19.2%; P=0.0043).ConclusionThe use of general anesthesia, especially nitrous oxide, for oocyte retrieval has an adverse effect on IVF outcome. This deleterious effect manifests itself only after embryo transfer and leads to lower pregnancy and delivery rates.

The significance of an early (premature) rise of plasma progesterone in in vitro fertilization cycles induced by a long protocol of gonadotropin releasing hormone analogue and human menopausal gonadotropins

AbstractObjective: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome Methods: Seven hundred eighty-six cycles were induced with GnRH-a and human menopausal gonodotropin (hMG) (“long protocol”). Plasma progesterone (PP) levels on the day of human chorionic gonadotropin (hCG) administration were divided into three groups: <0.9 ng/ml (Group A), 1–2 ng/ml (Group B), and >2 ng/ml (Group C). We also analyzed the pregnancies achieved in our egg donation protocol in relation to the PP levels of each donor on the day of hCG administration. Results: Group A involved 525 cycles, Group B had 223, and Group C had 38. The overall pregnancy rate per egg transfer was 19.2%, with the highest for Group A (22.3%), declining for Groups B (14.3%) and C (7.9%) (A = B = C; P<0.005). The embryo implantation rate was found to be negatively correlated with the PP levels on the day of hCG administration. In contrast, there was an opposite trend between PP levels and the chance of conception in 30 pregnancies achieved by egg donation. Conclusions: Since premature luteinization is very unlikely to occur under the conditions of this study, our findings suggest that an early PP rise has a negative impact on endometrial receptivity but not on egg and embryo quality.

Therapeutic maturation of endometrium in in vitro fertilization and embryo transfer

OBJECTIVE To provide an up-to-date review of studies that have examined the relative role of endometrial development in in vitro fertilization (IVF) and embryo transfer (ET) treatment in relation to the treatment outcome. DATA IDENTIFICATION The most important published studies and personal communications related to this topic have been identified through a computerized bibliographical search (MEDLINE). STUDY SELECTION Studies that have evaluated the endometrial maturation in IVF and ET treatment with respect to different treatment protocols of ovarian stimulation. Clinical trials exploring the efficacy of various combinations of hormonal supplementation that aim to improve the endometrial environment and treatment outcome. Publications and personal communications reporting a variety of treatment protocols and drugs utilized for the creation of artificial endometrial cycles in IVF treatment employing donated eggs. RESULTS Ovarian stimulation frequently adversely affects the process of endometrial maturation. Various kinds of hormonal supplementation, used in clomiphene citrate- and/or human menopausal gonadotropin (hMG)-stimulated cycles have not improved treatment outcome. Human chorionic gonadotropin or natural progesterone (P) supplementation administered after controlled ovarian stimulation with gonadotropin-releasing hormone and hMG effectively corrected the luteal phase defect and resulted in an improved conception rate. The endometrium of agonadal women is highly conducive to hormonal manipulation. All estrogen preparations used effectively promoted endometrial growth and proliferation. Natural P is superior to synthetic progestins for induction of receptive secretory endometrium. CONCLUSION The development of adequately receptive endometrium is a major factor determining the outcome of IVF and ET treatment.

Egg donation in an in vitro fertilization program: an alternative approach to cycle synchronization and timing of embryo transfer

A new flexible protocol for the induction of recipient endometrial cycles is presented. For stimulation of endometrial growth, a fixed dose of conjugated estrogens, 3.75 mg/d was employed. The duration of the proliferative phase varied from 9 to 14 days, thus being adjusted to match the length of the follicular phase of the donor. Embryo transfer was performed on the fifth day of progesterone administration. Four term pregnancies resulted from 12 treatment cycles. In the conception cycles, the hormonal support was continued until the luteal placental shift occurred, regardless of gestational age.

The treatment of benign breast disease with danazol.

Benign breast disease, aside from fibroadenomas and intraductal papillomas, frequently responds favorably to hormonal therapy. Although the use of estrogen, androgens, and progestogens often proves useful, danazol, in our hands, was found more consistently effective. Danazol, an impeded androgen derived from a progestogen, 17 alpha-ethinyltestosterone, was employed in doses of 100 to 400 mg/day for 3 to 6 months in the treatment of fibrocystic disease. This agent proved efficacious in eliminating nodularity in the majority of cases, with partial resolution in most of the others. Many women to whom surgery had been previously suggested were spared surgical interference because of a satisfactory response to danazol therapy.

Combined ovarian vein catheterization with ovarian stimulation in the diagnosis of androgen overproduction

A 28‐year‐old woman was evaluated for late onset secondary amenorrhea, progressive hirsutism and an elevated serum testosterone concentration. Her serum cortisol, androstenedione, dehydroepiandrosterone sulfate and 17‐hydroxyprogesterone levels were normal. Bilateral ovarian and adrenal vein catheterization demonstrated mild elevated testosterone and androstenedione levels in the right ovarian vein. Fifteen minutes after administering the intravenous injection of 5,000 IU human chorionic gonadotropin, there was a six and a half to sevenfold increase in the level of these two hormones in the right ovarian vein with no significant change in hormone levels from other sources. Based on the ovarian peripheral vein gradients obtained during venography following ovarian stimulation, the diagnosis of right ovarian hyperthecosis was made. This diagnosis could not have been reached without the combination of selective ovarian vein catheterization and ovarian stimulation. We recommend that this combined test, which may provide additional information on the source of the androgens in women with hyperandrogens, be performed in selected cases, when a virilizing tumor is suspected.

The use of PGE2 for induction of labor in parturients with a previous cesarean section scar

Controversy still dominates the discussion of the correct method for delivering patients with a previous cesarean section (C/S) scar. Although many have abandoned the slogan of “once a cesarean, always a cesarean”, repeat cesareans are still the rule in many institutions. We have abandoned this dogma, and are now advancing to new ideas and are promoting a new protocol. Nineteen post‐one cesarean section patients were induced on various indications by means of PGE2 pessaries. Close surveillance revealed no complications and 16 were delivered vaginally. All neonates had good Apgar scores, and all scars were found to be intact upon examination. We recommend cautious use of prostaglandins for selected post‐cesarean patients.

The inability of preovulatory ovarian scan to predict multifetal pregnancy occurrence in a follow-up of induction of ovulation with menotropins.

OBJECTIVE To establish the predictive role of preovulatory ovarian ultrasonography in the occurrence of multiple pregnancy after hMG and hCG treatment for anovulatory infertility. DESIGN Prospective. SETTING Outpatient Infertility Clinic. PATIENTS Ninety-five anovulatory women who conceived after gonadotropin therapy. INTERVENTION Induction of ovulation by hMG and hCG monitored by plasma E2 measurements and ovarian ultrasonography. MAIN OUTCOME MEASURES All follicles visualized on the day of hCG administration were recorded and divided into the following four groups: group I, 10 to 12 mm; group II, 13 to 15 mm; group III, 16 to 18 mm; and group IV, 19 mm and larger. The sonographic findings were statistically evaluated to 80 singletons and 45 multiple pregnancies. RESULTS No statistical correlation was found to exist between the number of follicles from the different groups and the number of fetuses. CONCLUSIONS The number and sizes of follicles visualized on the day of hCG administration have no predictive value regarding the occurrence of a multiple pregnancy.

Lack of correlation between hormonal blood levels and endometrial maturation in agonadal women with repeat implantation failure following embryo transfer from donated eggs.

Five women with ovarian failure who repeatedly failed to conceive following embryo transfer from donated eggs underwent endometrial development investigation. One endometrial biopsy was obtained on cycle days 19, 21, and 23 during three consecutive artificially induced cycles. All five patients had only early secretory changes on days 19 and 21. Histological evaluation on cycle day 23 revealed various developmental stages: two women had “in-phase” endometrium, two patients had adequately developed stroma but significantly retarded glandular maturation, and one women showed no progress. The histological findings were conclusive for a significant maturation delay and an impaired endometrial receptivity. There was a lack of correlation between the peripheral hormonal blood levels and the endometrial maturation.