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Biomedical subjects

A Hazout

Publications and source records attributed to A Hazout.

At least 19 recordsLinked to original sources

Coculture of embryos on Vero cells and transfer of blastocysts in humans.

Preliminary results are presented concerning the first clinical application of cocultures of human embryos. In the experimental group, the embryos were cultured and transferred on day 5 post-insemination. Blastocyst formation was not dependent upon the stimulation regimen. Long term or ultrashort stimulation of the ovaries after gonadotrophin releasing hormone analogue gave 55-60% blastocyst formation. Serum was not necessary to obtain blastocysts. When the embryos were cocultured, we observed an increase in the implantation rates per embryo in the pregnant patients. However, a real increase in the pregnancy rate per transfer was observed in a population of patients who had had repeated failures of embryo transfer. This observation is discussed as possibly bypassing an effect of uterine motility, but the overall beneficial effect has to be assessed in a double blind randomized study. It is probable that improvements will not be observed for all the indications for in vitro fertilization.

Animals

Controlled preparation of the endometrium with exogenous oestradiol and progesterone: a novel regimen not using a gonadotrophin-releasing hormone agonist.

In women having inactive ovaries, controlled preparation of the endometrium has been achieved with exogenous oestradiol and progesterone. We report on the feasibility and practicality of using a similar regimen for timing transfers of cryopreserved embryos in women whose ovaries have not been suppressed. A total of 91 women having cryopreserved embryos from previous in-vitro fertilization (IVF) attempts received 4 mg/day of oestradiol valerate, starting on cycle day 1 of spontaneous (n = 85) or induced (n = 6) menstruation. A single blood sample was obtained on cycle day 14 for the measurement of plasma progesterone, oestradiol and luteinizing hormone (LH). Vaginal administration of micronized progesterone (300 mg/day) was started on day 15. Cryopreserved embryos were transferred on day 17 or 18 provided that day 14 plasma progesterone remained < or = 0.5 ng/ml, thereby confirming the absence of spontaneous ovulation prior to the administration of exogenous progesterone. Out of 91 cycles studied, plasma progesterone was found to be elevated (> 1 ng/ml) in only three (3.2%). Of the 88 scheduled transfers, 31 did not take place because no embryo survived thawing. In the remaining 57 cycles, 116 embryos were transferred resulting in 10 pregnancies, giving pregnancy and embryo implantation rates of 17.5 and 8.6% respectively. When a positive beta human chorionic gonadotrophin (HCG) titre was obtained, supplementation with oral oestradiol and vaginal progesterone was continued until placental autonomy was achieved. Of the 10 pregnancies, five (50%) were lost during the first trimester (biochemical, n = 1; miscarriage, n = 3; ectopic, n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous

Controlled preparation of the endometrium with exogenous estradiol and progesterone in women having functioning ovaries.

OBJECTIVE: To determine if controlled preparation of the endometrium with exogenous estradiol (E2) and progesterone (P) could be achieved in women retaining their ovarian function without requiring prior ovarian suppression with a long-acting agonist of gonadotropin-releasing hormone (GnRH-a). DESIGN: Prospective feasibility study of a new simplified hormone regimen for preparation of endometrium receptivity. Six volunteer women received transdermal E2 and vaginal P without prior suppression of their ovarian function with GnRH-a. The control group consisted of previously reported cases receiving GnRH-a and E2 and P. SETTING: Academic tertiary care institution. PATIENTS: Six volunteer women. MAIN OUTCOME MEASURES: Participants received transdermal E2 and P after a regimen designed to duplicate the plasma E2 and P levels seen in the menstrual cycle. INTERVENTION: Endometrial biopsy. RESULTS: Plasma luteinizing hormone increased to surge levels in one woman on day 11, in two on day 12, and on day 14 in the remaining three women. No follicular growth was noticed on ultrasound, and no increase in plasma P occurred before the onset of P administration on day 15. Day 20 endometrium specimens showed early secretory changes as previously reported in women deprived of ovarian function receiving similar hormonal treatment. CONCLUSIONS: Our results indicate that controlled preparation of the endometrium can be achieved with exogenous E2 and P without prior ovarian suppression with a GnRH-a in women having functioning ovaries. Hence, administration of exogenous E2 and P appears to be a viable simpler alternative to the combined administration of GnRH-a and exogenous E2 and P, which avoids the side effects and the cost of GnRH-a.

Adult

Correlation between follicular fluid content and the results of in vitro fertilization and embryo transfer. III. Proteoglycans.

Using a specific proteoglycan (PG) radioimmunoassay (RIA) in which human cartilage antiserum was directed against the PG protein core, the PG content of follicular fluid (FF) obtained from 42 women undergoing in vitro fertilization (IVF) and embryo transfer (ET) was studied as a function of IVF-ET outcome. Inhibition curves of purified PG cartilage preparations were parallel to those of large and small nonstimulated follicles and follicles that had been stimulated by a luteinizing hormone-releasing hormone (LHRH) agonist, d-tryptophan-6 (Decapeptyl: D-Trp6 analogue, Beaufour Laboratories, IPSEN Biotech, Paris, France), and human menopausal gonadotropin (hMG). While FF levels of immunoreactive PG-like material (Ir-PG) did not differ according to IVF-ET outcome, highly significant negative correlations were obtained between FF 17 beta-estradiol levels and FF Ir-PG levels in oocyte groups where pregnancy was obtained, i.e., oocytes were fertilized and cleaved, and pregnancy followed either for each ET or for one of two embryos reimplanted. The correlation persisted but weakened when all groups were pooled together. No correlation was observed between FF Ir-PG and progesterone. RIA or bioassay showed a positive correlation between FF inhibin and Ir-PG for the group in which each ET led to a pregnancy. Ir-PG concentrations were significantly greater in smaller than in larger follicles collected from untreated women. Upon induction of ovulation with either pure follicle-stimulating hormone (FSH), FSH + human chorionic gonadotropin (hCG), or D-Trp6/hMG + hCG, this difference no longer appeared. These results indicate that the reduction of Ir-PG concentrations constitutes an index of follicular maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cartilage

Correlation between follicular fluid content and the results of in vitro fertilization and embryo transfer. II. Inhibin and aromatase inhibitor activity.

The inhibin content and aromatase inhibitor activity (AIA) of 72 follicular fluids (FF) obtained from 42 women undergoing in vitro fertilization (IVF) and embryo transfer (ET) were studied as a function of IVF ET outcome. Inhibin levels were determined by bioassay (BA) and RIA; AIA was measured by BA. The inhibin content of follicles characterized as immature by their estradiol (E2) levels and E2/progesterone (P) ratios was significantly lower (P less than 0.05) than that of mature follicles (i.e. leading to pregnancy). The mean AIA for mature follicles were significantly lower than AIA in groups where pregnancy was not obtained. AIA for follicles from which a pregnancy was obtained for each ET was also significantly lower than that in FF characterized as immature of hypermature. The highest E2/AIA and inhibin BA/AIA ratios were associated with the highest incidence of successful IVF ET outcome. No correlation was found between AIA and inhibin, on the one hand, and E2, delta 4-androstenedione, E2/P, and PRL, on the other. However, a positive correlation was found between inhibin (RIA and BA) and P, reflecting the production of inhibin by granulosa cells during luteinization. These studies allowed us to conclude that FF inhibin levels do not differ according to IVF ET outcome, but are an index of follicular maturation. AIA not only constitutes an index of follicular maturation and granulosa cell luteinization, but is of predictive value for IVF ET outcome as E2/AIA and inhibin BA/AIA ratios.

Adult

An obstetric analysis of fifty consecutive pregnancies after transfer of cryopreserved human embryos.

This report describes the obstetric outcome in 50 pregnancies resulting from the transfer of human embryos that had been cryopreserved for up to 2 years. The duration of cryopreservation did not influence the pregnancy rate after thawed embryo transfer. Thirty-one babies have been born from 28 pregnancies and a further seven pregnancies are currently in the second and third trimesters. Twenty-eight percent of the pregnancies failed to progress beyond the first trimester. One pregnancy was terminated at 22 weeks' gestation because of severe fetal malformation. Important antenatal events included premature uterine activity in six patients although only one patient with a singleton pregnancy ultimately was delivered prematurely. Retroplacental hemorrhage occurred in four patients but was of clinical consequence in only one. There was a high incidence of breech presentation at term in singleton pregnancies (12%). The cesarean section rate in this series was 21%. An international registry of cryopreserved pregnancies would facilitate data collection in this relatively new clinical field.

Adult

[Simulation of ovulation using two types of LH-RH agonists].

Luteinizing hormone-releasing hormone (LH-RH) agonists are being increasingly used in ovulation stimulation protocols in IVF programs. The results of two methods of utilization of LH-RH agonists are compared. There was difference in the ovarian response on the day of human chorionic gonadotropin (hCG) higher in the short protocol (69% vs 56%, P less than 0.001). The ongoing pregnancy rate per treatment cycle was similar in both groups (18% in the long protocol and 16% in the short protocol).

Chorionic Gonadotropin

Correlation between follicular fluid content and the results of in vitro fertilization and embryo transfer. I. Sex steroids.

The steroid content of 72 follicular fluids (FF) obtained from 42 women subjected to ovulation induction with the luteinizing hormone-releasing hormone analogue D-Trp6 and human menopausal gonadotropin was studied in terms of the evolution of in vitro fertilization (IVF) and embryo transfer (ET) results. The FF were classified into several categories based on oocyte evolution. Individual values of FF estrone and estradiol (E2), as well as androstenedione and testosterone could not be correlated with ET outcome. However, FF progesterone (P) levels for follicles leading to pregnancy were significantly lower when compared with those in the other categories. The correlation between the E2/P ratio and E2 permitted the definition of a band wherein IVF-ET outcome was successful and enabled the characterization of different functional follicular maturational states.

Androstenedione

Influence of different stimulation treatments on oocyte characteristics and in-vitro fertilizing ability.

A retrospective analysis was performed in order to compare the number and quality of oocytes recovered in in-vitro fertilization cycles according to different protocols for ovarian stimulation. Treatments including a gonadotrophin-releasing hormone agonist (GnRHa), either decapeptyl or buserelin, were associated with the recovery of more oocytes (6.0-7.2%) than treatments without GnRHa (3.7-4.8%). However, the mean number of normal embryos per patient yielding oocyte(s) was comparable between cycles stimulated with or without GnRHa (2.4-2.7), except in those cycles programmed with norethisterone and gonadotrophins (1.7). There was no difference in the rates of immature or atretic oocytes between stimulation treatments. Following clomiphene and human menopausal gonadotrophin treatment there was a lower rate of fractured zona oocytes, higher rates of fertilization and normal growth of fertilized eggs than after any other treatment. The proportion of normal embryos per recovered oocyte was inversely related to the degree of ovarian response in most of the stimulation treatments. Most of the abnormal embryos contained more than two pronuclei in cycles without GnRHa administration and exhibited polynucleated blastomeres in cycles treated with buserelin or decapeptyl. In conclusion, the use of GnRHa and gonadotrophins for ovarian stimulation increased the mean number of recovered oocytes, but did not increase the mean number of embryos able to develop.

Adult

Embryo quality and uterine receptivity in in-vitro fertilization cycles with or without agonists of gonadotrophin-releasing hormone.

The proportion of abnormal oocytes or embryos per recovered oocyte in in-vitro fertilization (IVF) cycles had no influence on the occurrence of pregnancy following the transfer of normal embryo(s) derived from oocytes capable of fertilization. There were more implantations per transferred embryo in stimulated IVF cycles using long-acting buserelin (30.0%) compared with short-acting decapeptyl (17.3%) or no gonadotrophin-releasing hormone agonist (GnRHa, 15.2%) treatments. However, the chances of implantation per embryo transferred being in excess of one in patients who became pregnant tended to be higher in non-GnRHa (23.5%) compared to buserelin- (16.4%) or decapeptyl- (13.3%) treated IVF cycles. Moreover, frozen--thawed embryos had a higher implantation rate (P less than 0.05) when originating from IVF cycles without GnRHa (11.7%) compared to GnRHa-treated cycles (buserelin, 4.3%; decapeptyl, 5.9%). It can be concluded that GnRHa associated with gonadotrophins produced embryos of a poorer aptitude for development than stimulation treatments without GnRHa. The clinical efficacy of GnRHa in IVF--ET cycles could be the result of an improved uterine receptivity to the transferred embryos.

Adult

Comparison between flare up and down regulation effects of luteinizing hormone-releasing hormone agonists in an in vitro fertilization program.

Luteinizing hormone-releasing hormone (LH-RH) agonists are being increasingly used in ovulation stimulation protocols in IVF programs. The results of two methods of utilization of LH-RH agonists are compared. In the long protocol, gonadotropin stimulation was commenced only after a preliminary period of pituitary desensitization with LH-RH agonist. In the short protocol, exogenous gonadotropins were administered shortly after the start of LH-RH agonist therapy, benefiting from the gonadotropin flare up effect. One hundred eighty-six patients were equally divided between the two treatments. There was no difference in the ovarian response on the day of human chorionic gonadotropin (hCG) or the number of mature oocytes recovered. The cleavage rate of mature oocytes was higher in the short protocol (70% versus 56% P less than 0.01). The ongoing pregnancy rate per treatment cycle was similar in both groups (18% in the long protocol and 16% in the short protocol). Analysis of the luteal phases revealed a trend for higher progesterone values in the long protocol although this was only significant on the 2nd day following oocyte retrieval. As the clinical results were similar, other factors should be taken into account when deciding therapy. These include patient convenience, cost, and side effects. Other schedules of ovulation stimulation with LH-RH agonists are discussed.

Adult

Selective oocyte retrieval: a new approach to ovarian hyperstimulation.

Selective oocyte retrieval is a new approach to ovarian hyperstimulation (OHS) that prevents side effects of OHS and multiple pregnancies by puncturing most of the ovarian follicles 35 hours after hCG administration as in an IVF program. The remaining intact follicles can still result in a singleton or twin pregnancy. In three patients who presented a multiple follicular development, this technique resulted in two pregnancies; moreover, the retrieved oocytes were fertilized and the embryos frozen.

Female

LHRH agonists in IVF: different methods of utilization and comparison with previous ovulation stimulation treatments.

LHRH agonists are being increasingly used in ovulation stimulation protocols in IVF programmes. We have compared the results of two methods of utilization of LHRH agonists. In the long protocol, gonadotrophin stimulation was only commenced after a preliminary period of pituitary desensitization with LHRH agonist. In the short protocol, exogenous gonadotrophins were administered shortly after the start of LHRH agonist therapy, benefiting from the gonadotrophin flare-up effect. One-hundred-and-eighty-six patients were divided equally between the two treatments. There was no difference in the ovarian response on the day of HCG or the number of mature oocytes recovered. The cleavage rate of mature oocytes was higher in the short protocol (70, versus 56, P less than 0.01). The ongoing pregnancy rate per treatment cycle was similar in both groups (18, in the long protocol and 16, in the short protocol). Analysis of the luteal phases revealed a trend for higher progesterone values in the long protocol although this was only significant on the second day following oocyte retrieval. As the clinical results were similar other factors should be taken into account when deciding therapy. These include patient convenience, cost and side-effects. Other schedules of ovulation stimulation using LHRH agonists are discussed.

Female

Improvements in ovarian stimulation for in vitro fertilization.

What are the major improvements in stimulation over recent years? The stimulated cycle has completely superseded the natural cycle since this is the only method of obtaining several embryos. In conventional stimulation, despite an enormous body of literature, no single treatment modality has emerged as superior to other forms of therapy. Undoubtedly it is the experience and habits of individual IVF teams that determine the success of one or another method. Therefore programmed stimulation is an improvement in that it introduces the factors of convenience and simplicity while retaining the clinical efficacy of stimulation by conventional treatment. The analogues of LHRH are still in an early phase of development, but they appear to be associated with a low cancellation rate even in previous poor-responders. Furthermore, preliminary results seem to indicate that this is the first development since the widespread adoption of follicular stimulation, which is associated with an increased pregnancy rate. We are currently involved in trying to associate programmed stimulation and analogue treatment in a bid to combine the advantages of both therapies. Finally, embryo cryopreservation must be mentioned. There is no point in refining our stimulation protocols to obtain many embryos if those surplus to immediate requirement are disposed of. Cryopreservation offers the means of maximizing the pregnancy potential of a single IVF cycle while reducing the possibility of multiple pregnancy.

Embryo, Mammalian

One year's experience with programmed oocyte retrieval for IVF.

We have previously described a simplified form of ovulation stimulation for IVF in which the day of presumed oocyte retrieval is determined several weeks in advance. This paper retrospectively analyses this technique in 296 unselected patients over a one year period to assess if the method is suitable for routine use in an IVF programme. Oocyte retrieval was performed on the predetermined day in 70% of patients commencing stimulation. In the remainder, the presumptive day of oocyte retrieval was modified, or the cycle was cancelled. Compared with 356 patients undergoing a comparable classically monitored IVF stimulation during the same period, there was no significant difference in the cancellation rate of cycles prior to oocyte recovery, in the numbers of oocytes or embryos obtained or in the pregnancy rate between the two populations. It is concluded that programmed oocyte retrieval does not have a deleterious effect on the success rate of IVF compared with classical clomiphene citrate/HMG stimulation and it considerably facilitates the administration of an IVF programme.

Clomiphene

Various techniques for oocyte recovery in an in vitro fertilization and embryo transfer program.

Oocyte recovery in an in vitro fertilization and embryo transfer (IVF-ET) program can be performed by laparoscopy or by sonography. Most IVF teams use either one or the other of these methods. In Clamart, we undertook 407 IVF attempts from September 1983 to March 1984, 225 by laparoscopy under general anesthesia, 97 by laparoscopy under local anesthesia, and 85 by sonography. Excluding the recovery techniques, all aspects of the program (ovulation monitoring, culture, and transfer) were identical in order to study the effects of the anesthesia and the ultrasound. We did not find any significant difference in pregnancy rates, inclusive of biochemical pregnancies, among these three recovery methods, although ultrasonically guided puncture gave fewer follicles, oocytes, and embryos than laparoscopy.

Adult

[Amniofetography].

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Amniocentesis