Biomedical subjects
J G Schenker
Publications and source records attributed to J G Schenker.
Stress and human reproduction.
The interaction between emotional stress and infertility has been investigated for many years. Many infertile couples show marked stress during infertility evaluation and treatment. Most of the investigations that were performed during the last two decades show that in the majority of cases stress is the result and not the cause of infertility. The biological interaction between stress and infertility is the result of the action of stress hormones at the brain level, especially on the hypothalamus-pituitary and on the female reproductive organs. Stress hormones such as catecholamines (adrenalin, nonadrenaline and dopamine) and the hypothalamic-pituitary-adrenal axis interact with hormones which are responsible for normal ovulatory cycles: i.e., gonadotropin releasing hormone (GnRH), prolactin, LH and FSH. Endogenous opiates and melatonin secretion are altered by stress and interfere with ovulation. Sympathetic innervation of the female reproductive system provides routes by which stress can influence fertility at the of the sex organs level. Infertility causes stress which is aggravated as time passes and the couple remains infertile. Among the causes of stress are the couple's isolation, life with unrealized potential and unborn child, disruption of day-to-day life during infertility evaluation and treatment, and the couple's feeling that they do not have control of their own lives. The IVF program is considered by many as the final step for the evaluation of the couples fertility potential, hence, couples participating in an IVF program are highly stressed, especially after a failed IVF cycle.
[AIDS in women and pregnancy: gynecological and perinatal aspects of AIDS].
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Enhancing in vitro fertilization of mouse oocytes by partial zona pellucida digestion.
This work was undertaken in order to evaluate the effect of partial zona digestion on fertilization in vitro of mouse oocytes and assess zona surface changes induced by the procedure. Three hundred forty-six oocytes allocated for treatment were exposed to Ham's F-10 medium supplemented with 0.5% Pronase for either 3 min (188 oocytes) or 5 min (158 oocytes); 324 oocytes served as controls. Oocyte losses incurred as a result of the procedure were small (15 oocytes; 4.3%). Control and Pronase-treated oocytes were each divided into four subgroups and inseminated with 5 x 10(5), 5 x 10(4), 5 x 10(3), or 5 x 10(2) sperm cells/ml. Fertilization was assessed 8 hr following insemination by the appearance of two pronuclei and development to the two- to four-cell stage the following day. The morphology of the zona pellucida following Pronase treatment was assessed by phase-contrast and scanning electron (SEM) microscopies performed immediately after treatment. Fertilization rate of control oocytes was 80% at a sperm concentration of 500,000/ml and gradually declined to approximately 30% at 500 cells/ml. In contrast, treated oocytes inseminated with 500 sperm cells/ml demonstrated a normal rate of fertilization. At this low sperm concentration the longer Pronase treatment was significantly (P less than 0.05) more efficient in enhancing fertilization (69 and 88% for 3 and 5 min of Pronase treatment, respectively). Polyspermic fertilization was not observed in any of the subgroups. Phase-contrast microscopic examination of oocytes at the time of Pronase treatment showed an initial swelling of the zona pellucida for 30-60 sec with a time-dependent increase in its transparency.
Surrogate practice in Israel: suggestions for regulation.
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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.
Ovum donation: ethical and legal aspects.
The newer technologies of assisted reproduction offer the infertile couple a wide spectrum of choices according to their specific problem. A relatively newer technique is that of ovum donation, whose technology is now well established. However, as with other newer technologies, it has given rise to new dimensions of ethical and legal issues which have to date not been fully appraised. It is very difficult to find a legal consensus under international umbrella to the specific issues involved in ovum donation. This is due to the different cultural, religious, and time influence atmosphere prevailing in the various parts of the world. Each society should develop its own statutes on ovum donation. A frame of ethical guidelines should be established by international organizations that may help each society issue its own regulations.
Religious views regarding treatment of infertility by assisted reproductive technologies.
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Effects of melatonin on progesterone production by human granulosa lutein cells in culture.
OBJECTIVE: To test the hypothesis that melatonin modulates steroid synthesis in the human ovary. DESIGN: Granulosa lutein cells obtained from in vitro fertilization cycles were cultured in medium containing melatonin and human chorionic gonadotropin (hCG). RESULTS: Progesterone (P) secretion by granulosa lutein cells increased progressively in both basal and hCG-stimulated conditions, up to 96 hours in culture, plateaued at 144 and decreased thereafter. Melatonin (10(-7), 10(-9), 10(-11) M) had no effect on basal P or 17 beta-estradiol production. The addition of melatonin to the hCG-treated granulosa lutein cells significantly (P less than 0.05) potentiated the stimulatory effect of hCG on P production. The effect was most prominent after 144 and 196 hours of incubation. CONCLUSION: This observation suggests a role for melatonin in the intraovarian control of P production in the human ovary.
The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study.
OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or placebo were administered in a prospective randomized double-blind manner. PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. CONCLUSIONS: In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.
Seasonality in human reproduction: an update.
A seasonal distribution in human natural conception and birth rates has been consistently demonstrated by epidemiological studies in several geographical areas. Possible hypotheses abound to explain this seasonality. Though a seasonal effect on reproduction is well-documented and has been extensively investigated in mammals, information concerning the influence of seasonal variation and its mechanism on human and primate reproduction is scarce. Recent evidence suggests that deterioration in sperm quality during the host summer in sub-equatorial areas, may result in lower conception rates leading to a reduction in the birth rate in spring. In northern countries, however, in regions where a strong seasonal contrast in luminosity exists, activity of the anterior pituitary-ovarian axis and the conception rate are decreased during the dark winter months. In these areas, inversely, a peak in conception rate during summer leading to a maximum in birth rate in spring has been observed. It is believed that seasonality in the ovulation rate may cause this variability. However, changes in the quality of the ovum or in endometrial receptivity which may lead to a greater waste of ovulated eggs and peri-implantation conceptuses at specific times of the year, have also been suggested. These phenomena might have important implications for in-vitro fertilization and gamete intra-Fallopian transfer as well as infertility in general. The seasonal effects, which may influence primate and human fertility and reproduction and its possible mediators, are critically reviewed.
The Israel perinatal census.
A nation-wide perinatal census which included 22,815 deliveries was carried out. The cesarean section rate was 9.6% and the perinatal mortality rate was 13.5/1000. Using a logistic regression analysis the risk factors for cesarean section and for perinatal mortality were ranked. Breech presentation and one uterine scar were found to be the most important risk factors for cesarean section and breech presentation, maternal disease and multiple pregnancy for perinatal mortality. Low birth weight rate was 6.9% with nonsignificant differences between the various ethnic groups. The national cesarean section rate in breech presentation was 57.8%. It was performed mainly at the extremes of birth weight. From those with one previous cesarean section 55.1% delivered vaginally and 44.9% abdominally. The chance for vaginal delivery is higher (67.2%) providing the woman had delivered vaginally in the past. Comparison between primiparae and multiparae showed that preeclampsia, hypertension and diabetes mellitus were all significantly more frequent among older parturients and among primiparae.
Triplets are not so rare any more.
Triplet gestations present a considerable management challenge due to a high rate of antenatal, intrapartum and neonatal complications. The introduction of ovulation inducing agents resulted in a marked increase of these pregnancies. Consequently, triplet conceptions are not considered a rare phenomenon and have become almost routine high risk pregnancies. In our department the triplet gestation frequency increased 2-4 times in a 10 year period from a rate of 0.07-0.14% during 1978-84 to 0.28% of all deliveries in 1987. This high incidence of triplet deliveries results in a threefold increase in the frequency of triplet neonates and their associated complications. It is reasonable to assume that the wide application of various assisted reproductive techniques will result in continuous increase in the incidence of triplets which will in turn require coordinated management of a high risk pregnancy unit, delivery room and neonatal intensive care unit.
Ovulation induction in in vitro fertilization.
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The value of an electronic microcomputerized basal body temperature measurement device (Bioself) in in vitro fertilization cycles.
The Bioself 110 electronic basal body temperature (BBT) measurement device was employed in 18 women undergoing in vitro fertilization (IVF). This microcomputer-operated device records, charts and accurately analyzes the mean temperature measurements. These temperature recordings were used in addition to transvaginal ovarian sonography and serum estradiol and progesterone levels. The BBT rise correlated significantly (p < 0.0002) with progesterone elevation following human chorionic gonadotropin (hCG) administration. It is suggested that this electronic device may be used as an additional tool in the detection of premature progesterone secretion in IVF cycles.
The effect of a prolonged artificial follicular phase on endometrial development in an oocyte donation program.
Stretching the duration of an artificial follicular phase in an oocyte donation program facilitates greatly the synchronization between the donor and the recipient. In order to investigate the limits of such a prolonged endometrial preparation, 18 patients with ovarian failure were studied during 20 treatment cycles. These patients were prospectively and randomly divided into three groups (A, B, and C in eight, six, and six cycles respectively). All groups were treated with oral estradiol and estriol (at a 2:1 ratio), 4 mg/day for 21, 28, and 35 days, respectively. At this stage 50 mg/day of intramuscular progesterone was added for additional 7 days. Endometrial adequacy was evaluated by late follicular and midluteal endometrial biopsies. During treatment no patient suffered from breakthrough bleeding. The mean estradiol and progesterone levels during the follicular and luteal phases did not differ significantly between groups. All late follicular biopsies showed a normal proliferative endometrium with no signs of glandular cystic hyperplasia. The midluteal biopsy showed a secretory endometrium adequate for 18.6 +/- 1.8, 21.8 +/- 1.8, and 18.6 +/- 1.5 days in groups A, B, and C, respectively, with no significant glandular-stromal disparity. We conclude that an artificial prolonged follicular phase does not seem to affect adversely the endometrial preparation in an oocyte donation program.
HELLP syndrome--a syndrome of hemolysis, elevated liver enzymes and low platelet count--complicating preeclampsia-eclampsia.
The course of preeclamptic/eclamptic patients may be complicated by HELLP syndrome, a syndrome of intravascular hemolysis (H), elevated liver enzymes (EL) and low platelet count (LP). These patients typically present at early third trimester with epigastric or right upper quadrant pain, nausea and vomiting. They may present without the clinical signs of preeclampsia (hypertension and proteinuria or edema), thus an initial wrong nonobstetric diagnosis is not uncommon. The most frequent maternal complication is intravascular coagulopathy (30%). Placental abruption and acute renal failure are also common. Ten cases of maternal deaths were reported among 295 cases reviewed in the English language literature, while the perinatal mortality rate was 226/1000. The grave prognosis for mother and fetus warrants physician awareness in order to accomplish early diagnosis and proper management. This paper is a review of the literature in English.
The value of menotrophin treatment for unexplained infertility prior to an in-vitro fertilization attempt.
This work was undertaken in order to evaluate retrospectively the relative efficacy of ovulation induction by menotrophins and that of in-vitro fertilization and embryo transfer (IVF-ET) in the treatment of unexplained infertility. These two treatments were compared between two groups of patients: 87 couples undergoing 446 cycles of ovulation induction by menotrophins (group A) and 72 couples undergoing 108 cycles of IVF-ET (group B). A total of 30 and 20 pregnancies were achieved in groups A and B for a rate of 34 and 28% per patient, respectively. A similar cumulative pregnancy rate (CPR) was achieved for three cycles of ovulation induction (23%) and one cycle of IVF-ET (22%). The cumulative live birth rate (CLBR) in group A was 22% after three cycles and exceeded that of one IVF-ET cycle (17%). It is concluded that menotrophin treatment in unexplained infertility is highly beneficial and should precede an IVF attempt.