Aby Lewin

Artificially Induced Endometrial Cycles and Establishment of Pregnancies in the Absence of Ovaries

In eight women with ovarian failure, we induced histologically normal endometrial function during a preparatory cycle consisting of sequential administration of estrogen and progesterone. During a subsequent cycle, endometrial stimulation was synchronized with surrogate-embryo transfer performed on days 16 to 21. Among the eight women, two pregnancies were established by embryo transfer on days 18 and 19. In both women, ovarian tissue was absent, and these patients therefore serve as an in vivo model for the isolated effects of estrogen and progesterone on implantation and maintenance of pregnancy. Treatment with exogenous estrogen was mandatory up to the 11th week of gestation, and treatment with progesterone until the 18th to 22nd weeks. We conclude that it is biologically feasible to simulate the essential hormonal and endometrial milieu of a fertile menstrual cycle and early gestation solely by the administration of estrogen and progesterone. Days 18 to 19 of the cycle are recommended for successful embryo implantation with this treatment program.

Is the obstetric outcome of in vitro fertilized singleton gestations different from natural ones? A controlled study

OBJECTIVE To determine whether singleton IVF pregnancies carry adverse maternal or fetal outcome when compared with naturally conceived gestations. DESIGN An analysis of the obstetric outcome of singleton IVF pregnancies in comparison with matched, naturally conceived singleton controls. SETTING In vitro fertilization unit and obstetric service at a tertiary medical center. PATIENT(S) Two hundred sixty consecutive singleton IVF pregnancies and 260 naturally conceived singleton controls matched 1:1 for maternal age, parity, ethnic origin, and location and date of delivery. INTERVENTION(S) In vitro fertilization-ET. MAIN OUTCOME MEASURE(S) The rate of antenatal obstetric complications, nonvertex presentation, cesarean section, preterm labor, low birth weight, small and very small for gestational age, neonatal intensive care unit admissions, and perinatal mortality. RESULT(S) The rates of most antenatal complications were similar in both groups. Urinary tract infection was the only complication diagnosed significantly more frequently after IVF (7.3% versus 1.2%); however, the rates of severe urinary tract infection necessitating hospitalization were similar. The incidence of nonvertex presentation was also similar. The cesarean section rate was significantly higher among IVF patients (41.9% versus 15.5%). The rates of preterm labor, low birth weight, small and very small for gestational age, neonatal intensive care unit admissions, and perinatal mortality were comparable. CONCLUSION(S) When controlling for maternal age, parity, ethnic origin, and location and date of delivery, singleton IVF pregnancies do not carry an increased risk for prematurity, low birth weight, or maternal or fetal complications. Still, these pregnancies are associated with a high rate of cesarean sections.

The effect of coenzyme Q10 on sperm motility and function

In sperm cells, the majority of coenzyme Q10 (CoQ10) an energy promoting agent and antioxidant, is concentrated in the mitochondria of the midpiece, so that the energy for movement and all other energy-dependent processes in the sperm cell also depend on the availability of CoQ10. The reduced form of CoQ10-ubiquinol also acts as an antioxidant, preventing lipid peroxidation in sperm membranes. The objective of the study was to evaluate the effect of CoQ10 on sperm motility in vitro, after incubation with 38 samples of asthenospermic and normal motility sperm, and to evaluate the effect of CoQ10 administration in vivo in 17 patients with low fertilization rates after in vitro fertilization with intracytoplasmic sperm injection (ICSI) for male factor infertility. All 38 sperm samples from patients registered in our infertility clinic had normal concentrations and morphology. Of these, 16 patients had normal motility (mean 47.5%) and 22 patients were asthenospermic (mean motility 19.1%). Sperm samples were divided into four equal parts and incubated for 24 h in: HAMs medium alone, in HAMs medium with 1% DMSO and HAMs with 5 microM or 50 microM CoQ10. While no significant change in motility after incubation was observed in the samples with initial normal motility, a significant increase in motility was observed in the 50 microM CoQ10 subgroup of sperm from asthenospermic men, with a motility rate of 35.7 +/- 19.5%, as compared to 19.1 +/- 9.3% in the controls (P < 0.05). The 17 patients with low fertilization rates after ICSI were treated with oral CoQ10, 60 mg/day, for a mean of 103 days before the next ICSI treatment. No significant change was noted in most sperm parameters, but a significant improvement was noted in fertilization rates, from a mean of 10.3 +/- 10.5% in their previous cycles, to 26.3 +/- 22.8% after CoQ10 (P < 0.05). In conclusion, the administration of CoQ10 may result in improvement in sperm functions in selective patients. Further investigation into the mechanisms related to these effects is needed.

The value of ultrasonographic endometrial measurement in the prediction of pregnancy following in vitro fertilization

This work was undertaken for evaluation of the value of endometrial thickness as an early predictor for the success of in vitro fertilization (IVF). Endometrial changes were evaluated ultrasonographically in 47 women undergoing IVF. A high-dose gonadotropin protocol was used for induction of multiple follicular development. Thirty-seven women did not conceive following the procedure (group I), and 10 conceived (group II). Ultrasonographic endometrial measurements were performed repeatedly throughout the cycle. Serum 17 beta-estradiol and progesterone levels were evaluated concomitantly. Three consecutive growth patterns of the endometrium were observed. The first was a rapid one with a daily growth rate of about 0.5 mm from approximately 9 mm on day -3 to 12 mm on day +2 (day 0 being the day of human chorionic gonadotropin administration). The second phase, following follicular aspiration, showed a decrease in growth rate to about 0.1 mm per day until day +11, when a thickness of about 13 mm was measured. In group I growth was arrested from day +11 until menstruation, whereas in group II an accelerated growth rate of about 0.4 mm per day could be demonstrated from day +14 onward. Endometrial growth did not correlate with serum estradiol or progesterone levels. No conception occurred with an endometrial thickness below 13 mm on day +11. It is concluded that endometrial thickness follows a distinct pattern of growth in human menopausal gonadotropin-induced cycles and does not correlate with serum sex hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with breast cancer

OBJECTIVE Our purpose was to investigate the frequency of ovarian cysts in tamoxifen-treated breast cancer patients. STUDY DESIGN The study population included 95 consecutive tamoxifen-treated premenopausal and postmenopausal women with breast cancer who were followed up by the outpatient clinic at the Hadassah University Hospital between September 1990 and June 1992. Tamoxifen was administered orally (20 mg/day). All patients underwent a pelvic examination and vaginal ultrasonography with a 5 MHz vaginal probe. RESULTS During the study 11 of 95 tamoxifen-treated breast cancer patients (11%) had ovarian cysts. Five cysts were detected in postmenopausal women (6.3% of the postmenopausal women) and six in premenopausal women (37.5% of the premenopausal women). In postmenopausal and premenopausal women the mean tamoxifen treatment interval was 19.4 +/- 7.8 months (range 4 to 48 months) and 28 +/- 6.1 months (range 12 to 54 months), respectively (p = 0.41). In 8 of the 11 patients the ovarian cystic enlargement disappeared after cessation of tamoxifen treatment. Two patients underwent laparotomy because of persistent cysts and the third because of a rapidly growing myoma. The three cysts were found to be benign. CONCLUSION Ovarian cysts are a common side effect of tamoxifen treatment. The ovarian cysts can develop in tamoxifen-treated premenopausal as well as postmenopausal women with breast cancer. Most of the tamoxifen-associated cysts disappear after tamoxifen treatment is abandoned.

The role of estrogen support during the luteal phase of in vitro fertilization-embryo transplant cycles: a comparative study between progesterone alone and estrogen and progesterone support

OBJECTIVE To evaluate the possible role for estrogen supplementation to the P luteal phase support of GnRH agonists (GnRH-a)- and hMG-induced IVF-ET cycles. SETTING In vitro fertilization unit in a tertiary care university hospital. DESIGN A prospectively randomized study. PATIENTS One hundred consecutive patients undergoing ET after IVF were assigned into one of two luteal supplementation regimens. INTERVENTIONS In all patients enrolled in the study, ovulation was induced using the midluteal regimen for pituitary down regulation with GnRH-a followed by follicular stimulation with hMG. The first group received IM P 50 mg/d, as luteal phase support, starting the day of ET. The second group received the same dosage of P, combined with oral E2 valerate, 2 mg/d. Serum levels of P and E2 were monitored every 4 days for 16 days after ET. MAIN OUTCOME MEASURES Pregnancy rates (PRs) and live birth rates per ET. RESULTS No significant difference in E2 or P levels throughout the cycle was observed between groups. Similar PRs per ET and the live birth rates were also observed between group A and B (28% versus 26.5% and 78.6% versus 76.1%, respectively). CONCLUSION No advantage was found in the addition of E2 valerate to P luteal phase support of GnRH-a- and hMG-induced IVF-ET cycles.

Seasonal variability in fertilization and embryo quality rates in women undergoing IVF

OBJECTIVE IVF-ET provides unique controlled conditions for the study of seasonal influences on the human reproductive process. This study was designed to evaluate the effects of seasonality on fertilization rate, embryo quality, and conception rates. DESIGN A retrospective observational cohort study. A chart review of all individuals undergoing IVF-ET from 1988 to 1991 at our institution was performed. SETTING An assisted reproduction unit at a university-based tertiary medical center. PATIENT(S) 657 women, for a total of 1074 IVF-ET treatment cycles, were evaluated. From this population, we chose 305 women undergoing their first IVF-ET cycle for reasons of pure mechanical infertility. INTERVENTION(S) IVF-ET cycles. MAIN OUTCOME MEASURE(S) Seasonal variability in fertilization rates and quality-A embryo rates, and the correlation with the absolute number of light hours, as well as the influence of temperature, humidity, and other environmental parameters. RESULT(S) A significant seasonal variability in the fertilization rate and the quality-A embryo rate was demonstrated. The highest fertilization and quality-A embryo rates were observed during the spring and the lowest in the autumn. These changes correlated with the absolute number of light hours and its increment over time, but not with the temperature, humidity, or other environmental parameters. CONCLUSION(S) Seasonality seems to have a significant influence on the fertilization process and on the quality of the human embryos that are obtained in vitro, possibly because of the light/dark variations over time. If this finding is confirmed, these seasonal changes should be taken into account when evaluating infertility data and in everyday clinical practice.

The role of uterine straightening by passive bladder distension before embryo transfer in IVF cycles

AbstractPurpose: The present study investigated the effect of bladder distension on in vitro fertilization and embryo transfer (IVF-ET) results. Methods: The study comprised 796 patients after successful transvaginal oocyte pickup and IVF, who, on the basis of bladder filling for ET, were divided into two groups. In group E, 385 patients underwent ET with an empty bladder, and in group F, 411 patients underwent ET with a full bladder. Results: Sixty-four pregnancies were achieved in group E (16.6%), compared to 110 pregnancies in group F (26.8%, P=0.006). A similar pregnancy loss rate was observed in both groups, 13 in group E (20.3%) and 29 in group F (26.4%; P=NS). Conclusions: A significantly higher pregnancy rate was achieved with routine bladder distension before ET, probably attributable to the smooth and easy insertion of the ET catheter.

Hyaluronic acid can successfully replace albumin as the sole macromolecule in a human embryo transfer medium.

OBJECTIVE To examine the effect on pregnancy and implantation rates when highly purified, fermentation-based hyaluronic acid was the only macromolecule supplement to the transfer medium in a human IVF program. DESIGN Prospective randomized study. SETTING In vitro fertilization center in an academic medical institution. PATIENT(S) Eighty patients were included in this prospective randomized double blind study. Inclusion criteria were age </=35 years, the availability of at least three embryos eligible for transfer on day 3 after fertilization, and no more than three previous embryo transfer attempts. INTERVENTION(S) All embryos were cultured in P1 medium containing 10% synthetic serum substitute (SSS) until day 3. Patients were randomly allocated to two groups; in treatment group A (40 patients), embryos were transferred to P1 medium supplemented with 0.5 mg/mL hyaluronic acid for 5-10 min before their intrauterine transfer. In the control group B (40 patients), embryos were transferred, as routinely performed, in P1 medium containing 10% SSS. MAIN OUTCOME MEASURES Clinical pregnancy and implantation rates. RESULT(S) The mean age of the female partner was 28.7 +/- 3.3 years and 29.7 +/- 3.8 years for groups A and B, respectively. In group A, 103 embryos were transferred and in group B, 97 embryos were transferred for a similar mean number of 2.6 +/- 0.6 and 2.4 +/- 0.5 embryos/transfer, respectively. Twenty-five pregnancies were achieved in group A, and 21 pregnancies in group B. This led to a comparable clinical pregnancy and implantation rates of 62.5% and 34% as compared to 52% and 26.8% for groups A and B, respectively. CONCLUSION(S) Hyaluronic acid can successfully replace albumin as a sole macromolecule in a human embryo transfer medium and result in high pregnancy and implantation rates. The use of this supplement is an important step in the development of human embryo culture media free of blood-derived additives.

Artificial endometrial preparation for oocyte donation: the effect of estrogen stimulation on clinical outcome.

Morphologic studies of the endometrium have demonstrated that varying the duration of an artificial follicular phase (AFP) in women with ovarian failure did not adversely affect its developmental capacity. The aim of this study was to evaluate whether such manipulations of endometrial stimulation could influence the pregnancy rate in women undergoing oocyte donation (OD). Twenty-nine women were investigated in 51 cycles of OD. Endometrial preparation was performed with a fixed dose of micronized estradiol, 4 mg/day, administered for 5–35 days in accordance with oocyte availability. On the day of donation progesterone in oil, 50 mg/day, was added to the regimen. Oocytes were donated anonymously by patients undergoing routine in vitro fertilization. Fifteen clinical pregnancies were achieved, for a success rate of 29.4%. Using logistic regression analysis the success rate was found to be closely associated with the duration of estrogen stimulation. The pregnancy rate was 7.7, 52, and 7.7% after an AFP of 4–11, 12–19, and 20–29 days, respectively. It seems that for optimal results in an OD program, estrogen stimulation should be kept at between 12 and 19 days. These results also imply that, contrary to endometrial morphology, which seems to be tolerant to extreme AFP durations, functional receptivity is less permissive and is adversely affected by such manipulations.