Preparation of the human endometrium for implantation.
Explore the source record for details and available documents.
Embryo Implantation↗
Biomedical subjects
D Navot
Publications and source records attributed to D Navot.
An insight into early reproductive processes through the in vivo model of ovum donation.
To gain insight into early reproductive processes we have prospectively designed ovum donation protocols to elucidate several phenomena relating to embryo implantation and pregnancy sustenance. Artificial endometrial cycles with variable follicular phases were induced in 60 recipients by sequential estrogen and progesterone. A total of 964 oocytes were retrieved throughout 43 ovum donation attempts, for an average of 22.4 (range, 16-41) eggs/retrieval. The overall delivery rate per egg retrieval (donors and recipients combined) was 72.1% (31 of 43). The shortest estrogen stimulation (short follicular phase) resulting in ongoing pregnancies was 5 days in duration, while the longest (long follicular phase) was 35 days in duration before progesterone initiation. Utilization of variable length follicular phases, artificially extended the stage of endometrial receptivity to over 4 weeks. To assess the window of implantation, same age embryos were transferred onto endometrium of different maturational stages. Pregnancies were documented with embryo transfers between luteal day 1 (day 15) to luteal day 6 (day 20), extending the window of implantation in the human to at least 6 consecutive days. To evaluate the relative contribution of oocyte quality and endometrial receptivity to pregnancy outcome, common source ova were transferred onto endometrium with variable hormonal exposure. Despite the drastically different follicular phase estradiol levels and periods of exposure, similar delivery rates were attained in donor cycles (29.4%) and recipient cycles during short follicular phases (29.6%). Slightly higher delivery rates (39.4%) were observed with long follicular phases. The comparable pregnancy rates in donors and recipients are attributed to the common source oocytes regardless of endometrial stimulation.
Adult↗
The concept of uterine preservation with ovarian malignancies.
A 30-year-old woman with bilateral, recurrent, borderline papillary serous cystadenocarcinoma of the ovary was treated with bilateral oophorocystectomy and omentectomy with uterine preservation. Ten years later, through induction of an artificial endometrial cycle and ovum donation, she conceived twins and delivered two healthy infants. Staging exploratory laparotomy at the time of cesarean delivery was negative for malignancy. This case illustrates the value of uterine preservation for cases in which classical teaching has indicated hysterectomy with bilateral salpingoophorectomy.
Adult↗
High-resolution endovaginal ultrasonography of the endometrium: a noninvasive test for endometrial adequacy.
Endovaginal sonography of the endometrium demonstrates characteristic findings throughout the menstrual cycle. To correlate these findings with histologic criteria for normal endometrial development, we compared endometrial biopsies with ultrasonographic findings. Nineteen cycles were monitored in 18 women with ovarian failure whose endometrial cycles were induced exogenously by sequential transdermal 17 beta-estradiol (E2) and intramuscular progesterone. These subjects underwent ultrasonography of the endometrium prior to the day of progesterone initiation (luteal day +1) and continuing throughout the mid-secretory phase. On luteal day +1, ultrasonography characteristically demonstrated a multilayered endometrium consisting of a hyperechoic perimeter (endometrial-myometrial interface), a hypoechoic inner layer, and a hyperechoic midline (luminal interface). By luteal day +7, a gradual increase in echogenicity of the inner layer was detected, while the inner myometrium remained hypoechoic. Eleven of 19 cycles demonstrated a completely hyperechoic endometrium on luteal day +7 and also demonstrated normal stromal development on endometrial biopsies. Three patients who had endometrial biopsies consistent with their chronological development failed to demonstrate a hyperechoic endometrium by luteal day +7. All five biopsies that were histologically out of phase were detected by ultrasonography. Thus, ultrasonography demonstrated a sensitivity of 100% and a specificity of 62% for the detection of histologically normal endometrial development. Endometrial thickness could not be used to discriminate between biopsies that were normal (13 +/- 1.0 mm) and those out of phase (13.8 +/- 1.8 mm). Endometrial histology demonstrated asynchrony of glands and stroma in nine cases in which ultrasonography correlated with stromal, but not with glandular dating, suggesting that the increased echogenicity may reflect stromal edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The predictive value of zona-free hamster egg sperm penetration assay for failure of human in vitro fertilization and subsequent successful zona drilling.
The value of various sperm parameters and the zona-free hamster egg sperm penetration assay (SPA) in predicting human in vitro fertilization (IVF) failure and subsequent successful fertilization with zona drilling was assessed. In 19 couples, throughout 31 IVF cycles, a total of 153 oocytes failed to be fertilized. In subsequent 12 cycles with zona drilling, 33 of 131 (25%) were fertilized. The incidence of teratospermia and asthenospermia was significantly higher in the study group than in the control, 74% versus 32% and 42% versus 5%, respectively. Although the mean values for the performance of sperm in SPA and fertilization of human eggs after zona drilling were remarkably similar (28 +/- 6 versus 28 +/- 4), there was no correlation between individual parameters (r = 0.15). Thus, whereas male factor infertility is more likely to be associated with teratoasthenospermia, neither the SPA nor other sperm parameters have any predictive value for failure in IVF. In addition, no criterion of sperm function has yet been identified that would eliminate oligoteratoasthenozoospermic males from consideration of IVF with zona drilling.
Cervix Mucus↗
Preovulatory luteinization during induction of follicular maturation with menotrophin and menotrophin--clomiphene combination.
Late follicular phase levels of 17 beta-oestradiol (E2) and progesterone (P) in serum were studied during the induction of follicular maturation with human menopausal gonadotrophin (HMG) (n = 23) and HMG-clomiphene citrate (CC) (n = 18). For each patient one hormonal profile was studied between 6 days to 2 h before administration of human chorionic gonadotrophin (HCG). Ultrasonographic follicular measurement at the time of evaluation demonstrated preovoulatory ovarian follicles of various number and size in all patients studied. Sixteen endometrial biopsies were performed at the time of evaluation (eight for each subgroup), before HCG administration. Mean late follicular phase levels of E2 did not differ significantly between the two groups (436 +/- 348 and 475 +/- 267 pg/ml for the HMG and HMG-CC groups respectively). The mean progesterone levels in the HMG-CC group (1.233 +/- 0.67 ng/ml) was significantly higher than that for the HMG group of (0.86 +/- 0.55 ng/ml, P less than or equal to 0.04). The mean time interval between ovulation and HCG administration for the two groups was 2.5 and 2.4 days for the HMG and HMG-CC groups, respectively. In all eight biopsies taken from the HMG group, various stages of endometrial proliferation were demonstrated. Premature glandular secretory transformation and oedematous stroma were observed in three out of eight biopsy specimens obtained from the HMG-CC group. Taken together, these results demonstrate that subtle or full premature luteinization in the late follicular phase occurs more frequently with the use of HMG-CC for induction of follicular maturation.
Adult↗
Clinical evaluation of three approaches to micromanipulation-assisted fertilization.
Three different micromanipulation procedures were used to assist human fertilization in cases of severe male factor infertility. Zona drilling was performed either with acid Tyrode's solution, mechanically following zona softening with chymotrypsin, or by partial zona dissection. The fertilization rate was lowest in the zona drilling/acid Tyrode's group (7/40; 17.5%), although no differences between groups (zona drilling/chymotrypsin: 21/84, 25%; partial zona dissection: 31/143, 21.7%) were significant. The fertilization rate was significantly increased relative to untreated eggs from the same patients only in the partial zona dissection group (31/143, 21.7% versus 4/102, 3.9%). Oocyte damage occurred at a high rate as a result of zona drilling with acid Tyrode's solution (13/41, 37%). Embryonic development was compromised after zona drilling with chymotrypsin: only 7/12 (58.3%) of the fertilized oocytes cleaved, and the morphology of many of the cleaved embryos was abnormal. Although only 61% (16/26) of the diploid embryos resulting from partial zona dissection cleaved, the embryonic morphology of these embryos was comparable with controls. No pregnancies resulted from the transfer of manipulated embryos. We conclude that although zona manipulation increases the fertilization rate, losses due to oocyte trauma, low rates of diploid fertilization, low rates of cleavage, and a high frequency of abnormal cleavage reduce the number of embryos available for transfer.
Dissection↗
Ranking the risk factors for cesarean: logistic regression analysis of a nationwide study.
The risk factors that influenced the decision to perform cesarean were ranked in a nationwide census of deliveries conducted in Israel. The study encompassed 22,815 women who gave birth between November 1, 1983 and January 31, 1984 in the 30 maternity departments in the country; 2179 deliveries were by emergency cesarean. Multivariate stepwise logistic regression technique indicated that the most important risk factors affecting the decision were the presentation of the fetus and the presence of a uterine scar, followed in descending order by placenta previa or abruptio placentae, maternal disease, primiparity, low birth weight, twins, and advanced maternal age. The mother's ethnic background and type of hospital played an insignificant role in the decision-making process. The specific statistical method applied in this work permits listing the indicators that constitute risk factors for cesarean and provides the net effect of each factor on the decision-making process.
Cesarean Section↗
Luteal phase deficiency after completely normal follicular and periovulatory phases.
Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal folliculogenesis included: a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases.
Adult↗
Successful microsurgical removal of a pronucleus from tripronuclear human zygotes.
We have microsurgically extracted a pronucleus from 11 tripronuclear human zygotes under two different experimental conditions. One group of six zygotes was incubated in cytochalasin D for 30 minutes before manipulation. The remaining five zygotes were manipulated without preincubation in cytoskeletal relaxing agents. When cytoskeletal relaxants were used, all six embryos survived manipulation and cleaved. One embryo arrested spontaneously at the two-cell stage; all others cleaved to at least four cells, and one embryo reached the advanced morula stage. Of the five eggs manipulated without prior cytochalasin D and colcemid treatment, none survived for more than 30 minutes after manipulation. In none of the tripronuclear eggs was it possible to definitely identify the male pronuclei. Because development was interrupted for karyotyping, it is likely that these embryos would have otherwise continued to develop to more advanced stages. These results indicate that it is possible to microsurgically "epronucleate" tripronuclear human zygotes and obtain further development and that use of cytoskeletal relaxants facilities this manipulative procedure. However, because epronucleated embryos have significant developmental potential, chromosome studies are needed to confirm complete removal of a male pronucleus before such techniques can be applied clinically.
Cytochalasin D↗
The long-term predictive value of the zona-free hamster ova sperm penetration assay.
Three hundred sixty-nine infertile couples were followed for 2 to 5 years in a study designed to determine the clinical long-term predictive value of the zona-free hamster ova sperm penetration assay (SPA). Semen analysis (SA), SPA, and a full infertility workup were done in all cases, and only couples in whom the female had no evident cause of infertility were included in the study. During the follow-up period, 106 couples (29%) achieved a pregnancy. Sixteen percent of 131 men who had an SPA of 0%, 23% of 120 men with 1% to 19%, and 48% of 118 men who had a penetration of greater than 19% impregnated their wives 2 to 5 years after the assays. Significant difference in fertility prognosis was found between those who had an SPA greater than 19% and those with an SPA less than 20% (48% versus 20%). Sperm penetration assay greater than 19% was predictive of higher pregnancy rates in both oligospermic (41% versus 17%) and unexplained infertile couples (52% versus 24%). The specificity and positive predictive values of the SPA were higher than those of the SA (77% versus 57% and 48% versus 37%). These findings emphasize the value and importance of the SPA in determining the long-term fertility potential of men.
Animals↗
Estradiol and progesterone replacement regimens for the induction of endometrial receptivity.
Initiation of pregnancy in premature ovarian failure patients by use of donated oocytes fertilized in vitro requires establishment of a normal endometrial environment. We compared administration of estradiol (E2) and progesterone (P) by polysiloxane vaginal rings versus oral micronized E2 and P vaginal suppositories in 10 such patients. Serum E2 levels were similar between groups and similar to normally-cycling controls. With vaginal administration of E2, a burst effect was noted, with marked elevation 1 hour after insertion. The pattern with oral administration was more consistent, although marked conversion to estrone occurred. The P cylinder and suppositories delivered similar levels, with diminution of P in some patients with the cylinder. Despite apparent limitations, endometrial histology was normal after each cycle; both groups achieved pregnancies. Administration of E2 and P by polysiloxane vaginal rings achieved hormonal levels similar to oral micronized E2 and P vaginal suppositories. Endometrial biopsies after the stimulated cycle were appropriately mature.
Absorption↗
Serum follicle-stimulating hormone inhibition is a marker for preovulatory oocytes in in-vitro fertilization and embryo transfer.
A retrospective analysis was performed on 64 cycles stimulated with human menopausal gonadotrophin and/or pure follicle-stimulating hormone (FSH) and oestrogen (E2) levels. The increase in serum E2 on the day of HCG administration did not correlate (r = 0.05) with the number of preovulatory oocytes (preovs) or with an increase or decrease in serum FSH (r = 0.31). However, the change in serum FSH showed a significant correlation with the number of preovs (r = -0.95, P = 0.013). The probability of obtaining two or more preovs was relatively greater (1.47x) than that of other IVF patients, when there was a drop in FSH of 5% on the day of human chorionic gonadotrophin administration.
Chorionic Gonadotropin↗
Hormonal manipulation of endometrial maturation.
Three experimental protocols were devised to induce endometrial maturation in 12 women with ovarian failure. Each was planned to serve a dual purpose: to resolve a particular clinical situation related to synchronization between ovum donor and recipient and to answer a specific question about endometrial physiology. A fourth protocol of sequential estrace (2-6 mg/day) and progesterone (P4; 25-50 mg/day, im) simulating the 28-day natural cycle, served as a control protocol (18 cycles). A short follicular phase protocol consisted of only 6 days of estrogen (E) administration before addition of P4 (13 cycles). In the long follicular phase protocol (5 cycles), estrace was given for 3-5 weeks, and P4 administration was accordingly postponed. In 6 accelerated secretory transformation cycles, 150 mg/day P4 were administered, im, from day 15 onward. The adequacy of the induced endometrial cycles was evaluated by hormonal, morphological, and histochemical criteria relevant to endometrial normalcy and receptivity. Serum estradiol levels and the areas under the estradiol curves for the long and short follicular phase protocols differed significantly from those during the control cycles (P less than 0.005). Areas under the estradiol curves in the accelerated secretory transformation protocol yielded significantly higher P4 values than those in all other protocols (P less than 0.05). All biopsies in the 3 experimental protocols compared favorably with those of the control protocol. Glycocalyx intensity (periodic acid-Schiff) and the amount of galactose residues in the glycocalyx (Ricinus communis-I agglutinin) were greatest during the periimplantation interval. We conclude that a very short exposure of the human endometrium to E or, conversely, prolonged E stimulation will allow normal endometrial maturation with the addition of P4. Supraphysiological doses of P4 in the accelerated secretory transformation protocol significantly enhanced endometrial maturational processes.
Adult↗
The 1984 national perinatal census: design, organization and uses for assessing obstetric services in Israel.
A nationwide perinatal census was conducted in Israel, in which medical, social, ethnic and demographic information on all births that took place in Israel within a predefined 3-month period was collected. The present study is the first to include 22,814 births that took place in all the obstetric units in Israel. The perinatal mortality rate decreased from 23.7 in 1964-68 to 13 in 1983-84. The frequency of cesarean section deliveries almost doubled over the last decade, while the use of forceps decreased significantly and the use of vacuum extraction did not change. The rate of low birthweight, however, remained constant over the last two decades. The level of hospital care has been shown to be significantly associated with perinatal mortality. The Israeli Perinatal Census may be used to provide information needed for promoting priority objectives for pregnancy and infant health, such as improving health status, identifying risk factors, increasing public and professional awareness, and improvement in services by protecting mother and fetus.
Adult↗
Assisted reproductive technology. A clinical appraisal.
With the various types of reproductive technology now available, the overall pregnancy rates still are less than 25%. An increase in those rates would permit physicians to provide relief from infertility to a much larger population.
Embryo Transfer↗
Spontaneous luteinizing hormone (LH) surges are associated with more rapidly increasing estradiol (E2) and follicle stimulating hormone (FSH) in in vitro fertilization and embryo transfer.
In a retrospective analysis of 64 patients stimulated with human menopausal gonadotropin (hMG) and/or pure follicle stimulating hormone (FSH); 35 cycles with spontaneous luteinizing hormone (LH) surges were compared with 29 control cycles with respect to serum FSH and estradiol (E2) levels drawn on the day prior to and the day of human chorionic gonadotropin (hCG), approximately 16 hr after gonadotropin stimulation. FSH decreased significantly (P less than 0.05) in control cycles where two or more preovulatory oocytes (preovs) were obtained, in contrast to cycles with a spontaneous LH surge, where FSH increased irrespective of the number of preovs. The E2 increase in the LH surge cycles was significantly higher (P less than 0.05) than in the control cycles. However, the increase in E2 did not correlate with the change in FSH levels or with the number of preovs.
Chorionic Gonadotropin↗