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Biomedical subjects

F Olivennes

Publications and source records attributed to F Olivennes.

At least 55 records · Page 3Linked to original sources

Hormonal influence on the uterine contractility during ovarian stimulation.

High-frequency uterine contractions (UC) at the time of embryo transfer have been shown to hamper the outcome of in-vitro fertilization (IVF). As UC are postulated to be hormone-regulated, we aimed to investigate the role of plasma oestradiol and progesterone concentrations on UC during ovarian stimulation for IVF. A total of 59 women were studied on the day of administration of human chorionic gonadotrophin (HCG) and embryo transfer. Plasma oestradiol and progesterone concentrations were measured, and 5 min ultrasound scans of the uterus were digitized with an image analysis system to assess UC frequency and direction. Cycles were sorted according to whether progesterone concentrations on the day of embryo transfer were < or =100 (n = 34) or >100 (n = 25) ng/ml. On the day of HCG, UC frequency was similar in both groups at 4.5+/-0.2 and 4.6+/-0.3 UC/min (mean +/- SE) respectively. On the day of embryo transfer, UC frequency remained steady in the low progesterone group, whereas it decreased (3.5+/-0.2 UC/min) in the high progesterone group (P < 0.001), and was negatively correlated with progesterone concentrations (r = -0.56; P < 0.001). No influence of oestradiol on UC was noticed. These observations confirm the utero-relaxing effects of progesterone in the non-pregnant uterus and support the administration of progesterone before embryo transfer to increase tissue concentrations and improve the outcome of IVF.

Adult↗

Effect of gonadotrophin-releasing hormone (GnRH) antagonist during the LH surge in normal women and during controlled ovarian hyperstimulation.

OBJECTIVE: Several studies have suggested that GnRH is instrumental in triggering the LH surge. The present studies were performed to evaluate the effect of GnRH antagonist administration in women after the beginning of the LH surge. DESIGN: In study one, six normal cycling women were given a GnRH antagonist (20 mg Nal Glu s.c.) during an unstimulated cycle. Nal-Glu was administered when the LH level was higher than 10 U/l and associated with an oestradiol (E2) level higher than 730 pmol/l. In study two, a GnRH antagonist (3 mg Cetrorelix, ASTA-Medica, Frankfurt, Germany) was administered on day 8 of an IVF-ET cycle, in 157 women. Eighteen women among this cohort received the antagonist, when their LH level was higher than 10 U/l. RESULTS: In normal volunteers (study one), Nal-Glu was administered on day 13.7 +/- 1.4 (mean +/- SD) of the cycle when the LH level was 13.7 +/- 3.5 U/l with an E2 plasma level reaching 980 +/- 131 pmol/l. Twenty-four hours after administration of the antagonist, the LH surge had been interrupted in all subjects; it was postponed in three of the women, and abolished in the remaining three. LH levels fell by 68.5%, E2 by 42% and FSH by 53.2%. In study two, LH plasma levels 24 h after the antagonist administration fell by 94%. No premature ovulation occurred in any of the patients treated. Administering the antagonist before (n = 139) or during the LH surge (n = 18) made no statistically significant difference to the results of the IVF-ET attempt. CONCLUSIONS: Our results indicate that GnRH is required throughout the gonadotrophin surge in women, not only for the initiation but also for the maintenance of the LH surge. In addition, in our study, the suppression of the rise in LH, when the antagonist was given during the surge, had no detrimental impact on IVF-ET outcome. This suggests, if confirmed on a larger scale, that late follicular phase GnRH antagonist administration to prevent the LH surge in controlled ovarian hyperstimulation (COH) is a safe and useful treatment.

Adult↗

Computerized assessment of endometrial echogenicity: clues to the endometrial effects of premature progesterone elevation.

OBJECTIVE: To determine whether premature progesterone elevation affects the timing of hyperechogenic transformation of the endometrium during the early luteal phase of controlled ovarian hyperstimulation (COH) cycles. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Fifty-nine women undergoing 59 IVF-ET cycles. INTERVENTION(S): Patients underwent COH with a GnRH agonist and hMG. Endometrial echogenicity was assessed on the days of hCG administration, oocyte retrieval, and ET. Results are expressed as the extent of submyometrial hyperechogenic area in relation to the total endometrial surface as determined by a computer-assisted analysis system. Patients were sorted according to whether their plasma progesterone level exceeded 0.9 ng/mL (n = 26) or not (n = 33) on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial echogenicity. RESULT(S): On the day of hCG administration, the degree of endometrial echogenicity was similar in both groups (41% vs. 40%), but after hCG administration, it increased significantly faster in the high progesterone group than in the low progesterone group (70% vs. 63% at oocyte retrieval and 90% vs. 79% at ET, respectively). CONCLUSION(S): End-follicular phase elevation in plasma progesterone (>0.9 ng/mL on the day of hCG administration) was associated with a faster increase in endometrial echogenicity during the early luteal phase of COH cycles. This observation is consistent with the hypothesis that premature progesterone elevation hastens the secretory transformation of the endometrium.

Adult↗

Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation.

Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.

Adult↗

Pregnancies, growth and development of children conceived by subzonal injection of spermatozoa.

Subzonal injection of spermatozoa (SUZI) was one of the first micromanipulation techniques efficient in treating male factor infertility and unexplained in-vitro fertilization failures. The aim of this retrospective study was to evaluate the in-vitro development of embryos conceived by SUZI, the obstetric outcome, the rate of congenital malformations and subsequent follow-up in children. Fifty-five pregnancies were obtained between 1991 and 1994 (54 after fresh embryos were transferred and one after cryopreserved embryos were transferred). Among the 50 clinical pregnancies, there were seven miscarriages (14%) and two ectopic pregnancies (4%). Among the 41 resulting evolutive pregnancies, the discovery of one anencephaly led to a medical abortion. Forty deliveries including six twin pregnancies occurred, leading to the births of 45 live neonates and one stillbirth. The gender distribution of the offspring included 17 males and 29 females (ratio 0.59:1). Birth weight, length and head circumference were within the expected ranges. Two children presented a malformation: the first one had one thumb with congenital shelf and the second a polymalformative neurological syndrome. Growth curves were normal for all these children except one (weight above the 2 SD curve). Medical follow-up detected no pathological features in these children apart from a physical disability in one girl. In this small series a 4.2% rate of malformation was observed, particularly affecting the neural tube, in SUZI offspring. However, no firm conclusions can be drawn since the study was carried out on a small cohort. SUZI is no longer performed but these observations suggest that it is necessary to collect extensive data about children conceived by microfertilization.

Abortion, Spontaneous↗

Female and male human embryo growth rates are similar before the eight-cell stage.

OBJECTIVE: Our purpose was to assess the possible relationship between human embryo growth rates and sexual differentiation. STUDY DESIGN: We analyzed 142 conceptional in vitro fertilization and embryo transfer cycles undertaken in 137 women (151 embryos transferred) in which each embryo transferred led to a gestational sac. Embryos were sorted into three groups according to the number of blastomeres assessed just before embryo transfers < or = 3, 4, and > or = 5 blastomeres. RESULTS: Percentages of girls and boys remained roughly unaltered irrespective of the number of blastomeres observed just before embryo transfer: < or = 3 blastomeres, 45% and 55%; 4 blastomeres, 44% and 56%; and > or = 5 blastomeres, 45% and 55%, respectively (statistical power 90% at the 5% significance level). CONCLUSIONS: This indicates that embryo growth rates before the eight-cell stage are not related to the sex of the live-born infant, thereby dissuading the use of embryo growth rates in the appraisal of sex likelihood in regular in vitro fertilization-embryo transfer.

Blastomeres↗

Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome.

OBJECTIVE: To investigate whether the presence of cervical microorganisms, as detected on catheters used for ET, alters the outcome of IVF-ET. DESIGN: Prospective analysis. SETTING: The assisted reproduction unit of a hospital in Clamart, France. PATIENT(S): Two hundred seventy-nine controlled ovarian hyperstimulation (COH) cycles performed for IVF-ET. Inclusion criteria were a patient age of < or =38 years, a morphologically normal uterus, and > or =2 good-quality embryos transferred. INTERVENTION(S): The tips of catheters used for ruling out possible cervical obstruction before ET were subjected to quantitative (> or =10 colonies = positive culture group; <10 colonies = negative culture group) and qualitative microbial assessment. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): In 143 (51%) of 279 ETs, cultures were positive, predominantly for Escherichia coli (64%) and Streptococcus species (8%). Although data on patients, COH, and embryology were similar in both culture groups, clinical and ongoing pregnancy rates as well as implantation rates were significantly lower in the positive culture group than in the negative culture group (24% versus 37%; 17% versus 28%; and 9% versus 16%, respectively). CONCLUSION(S): The presence of microbial flora of the cervix on ET catheters is associated with poor IVF-ET outcome.

Adult↗

Are there still obstetric and perinatal benefits for selective embryo reduction of triplet pregnancies?

We present in this study the results of a retrospective analysis comparing a group of ongoing triplet pregnancies and a group of triplet pregnancies reduced to twins. These two groups were managed in the same way between January 1993 and April 1996 in hospital. Mean gestational age at birth was comparable in both groups of patients. Prematurity rate was lower in the reduced pregnancies group (62.5 versus 95.6%, P < 0.05). Severe prematurity (<32 weeks) was not different in the two groups. The percentage of Caesarean section was lower in the reduced group (23.5 versus 70.8%, P < 0.01). No significant difference was observed for perinatal mortality. Newborns of ongoing triplet pregnancies had a higher percentage (67.7 versus 86.8%) of hospitalization in the intensive neonatal care unit and a tendency towards lower birthweight. The differences observed in this study do not seem to represent a decisive benefit for reducing triplet pregnancies. Due to the progress in the management of multiple pregnancies and neonatal intensive care, we think that embryo reduction should no longer be justified by obstetric benefits but rather as a possibility offered to couples who could be confronted with the potential severe psychological, social and economic problems of triple births.

Adult↗

Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization.

To investigate the possible consequences of uterine contractions (UC) as visualized by ultrasound (US) on in-vitro fertilization (IVF)-embryo transfer outcome, we studied prospectively 209 infertile women undergoing 220 cycles of controlled ovarian stimulation. Inclusion criteria were age < or = 38 years, a morphologically normal uterus, and at least three good quality embryos transferred. Just before embryo transfer, women underwent 5 min digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone and oestradiol concentrations were measured. Four groups were defined according to UC frequency: < or = 3.0 (n = 53), 3.1-4.0 (n = 50), 4.1-5.0 (n = 43), and > 5.0 (n = 74) UC/min respectively. Patients, controlled ovarian hyperstimulation and embryology characteristics were comparable in all groups. A stepwise decrease in clinical and ongoing pregnancy rates as well as in implantation rates occurred from the lowest to the highest UC frequency groups (53, 36, 21; 46, 32, 20; 23, 19, 10; and 14, 11, 4%; P < 0.001). Plasma progesterone and UC frequency were negatively correlated (r = -0.34, P < 0.001). Direction of UC did not affect embryo transfer outcome. As this study was controlled strictly for confounding variables and UC were assessed objectively by a computerized system, its results indicate that high frequency UC on the day of embryo transfer hinder IVF-embryo transfer outcome, possibly by expelling embryos out of the uterine cavity. The negative correlation between UC frequency and progesterone concentrations supports the uterine relaxing properties of progesterone.

Chorionic Gonadotropin↗

The use of a GnRH antagonist (Cetrorelix) in a single dose protocol in IVF-embryo transfer: a dose finding study of 3 versus 2 mg.

New gonadotrophin-releasing hormone (GnRH) antagonists, which allow suppression of luteinizing hormone (LH) surges, have recently become available. We compared in this study the results of a single administration of 3 versus 2 mg Cetrorelix in 65 patients undergoing ovarian stimulation and in-vitro fertilization (IVF). The GnRH antagonist (Cetrorelix) was non-randomly administered at a dose of 3 mg (34 patients) or 2 mg (32 patients) on day 8 of the stimulation cycle. In the case of slow follicular development, the injection was delayed until oestradiol reached 400 pg/ml. No difference was observed in the decrease in LH and in oestradiol secretion between the 3 and the 2 mg groups, but the LH secretion was suppressed for a shorter time in the 2 mg group. No LH surge was observed in the 3 mg group, while one surge (3%) and one significant rise in LH were observed in the 2 mg group. No significant difference was observed in IVF results in the two groups of patients. This study demonstrates that a single injection of 3 or 2 mg successfully prevents LH surges for at least 3 days in all the patients treated. The LH rises in the 2 mg group led us to choose the 3 mg dose as a safer dose in our single administration protocol.

Adult↗

[In vitro fertilization and sperm intracytoplasmic injection: psychological repercussions for the couple].

The aim of the study was to assess the psychological repercussions of IVF + ICSI on the male partner of infertile couples and on the couples and on the couple itself. The preliminary work has been done on the 23 couples in the waiting list of an ICSI cycle in A. Beclere hospital in Clamart. All couples respond to the same questionnaire. The two members of the couples were present in a semi-structured interview by 2 clinical psychologists. This ICSI scheme requires a complete change about the biological paternity. For infertile men, getting embryos work as a real reparation of their wounded ego, and the guilt goes from the man to the women when embryos are obtained. This study shows that infertile couples involved in IVF + ICSI have not the same concerns that doctors. Genetic abnormality transmission is not mentioned. On the opposite the male patients are strongly concerned by obtention of embryos which restore their fertility power. At this stage, female patients have to prove by carry out a pregnancy that they are as "good" as their partner.

Adult↗

Consequences of premature progesterone elevation on the outcome of in vitro fertilization: insights into a controversy.

OBJECTIVE: To investigate whether the consequences of premature P elevation on IVF-ET outcome are modulated by the quality of the ovarian response to controlled ovarian hyperstimulation (COH). DESIGN: Retrospective analysis. SETTING: Assisted Reproduction Unit, Clamart, France. PATIENT(S): One thousand twelve women undergoing 1,189 IVF-ET cycles. INTERVENTION(S): Patients underwent COH with a time-released GnRH agonist and hMG. The ovarian response to COH was classified as strong (< or = 50 hMG ampules, peak E2 levels > 2,500 pg/mL, and > or = 10 mature oocytes; n = 340), weak (> 50 hMG ampules, peak E2 levels < or = 1,500 pg/mL, and < or = 5 mature oocytes; n = 285), or intermediate (remaining cases; n = 564). The IVF-ET outcome in each group was analyzed according to whether or not plasma P levels exceeded 0.9 ng/mL. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs). RESULT(S): Clinical PRs were similar irrespective of low or high P levels in the strong (30% and 34%, respectively) and intermediate (31% and 30%, respectively) groups. However, in the weak group, P levels > 0.9 ng/mL were associated with lower PRs (3.2% and 23%, respectively). CONCLUSION(S): In the presence of an adequate response to COH, P levels > 0.9 ng/mL were not associated with lower PRs, indicating that good embryo quality may compensate for the adverse endometrial effects of P. Conversely, when the response to COH was weak, premature P elevation led to drastically reduced PRs.

Adult↗

Premature progesterone elevation spares blastulation but not pregnancy rates in in vitro fertilization with coculture.

OBJECTIVE: To clarify whether embryo development to the blastocyst stage may be affected by premature P elevation during controlled ovarian hyperstimulation (COH) for IVF-ET with embryo coculture. DESIGN: Retrospective study. SETTING: Tertiary care infertility center. PATIENT(S): One hundred thirty-one women undergoing 153 IVF-ET cycles with embryo coculture. INTERVENTION(S): Patients underwent COH with GnRH agonist and hMG. Embryos were cocultured up to the blastocyst stage. According to plasma P levels on the day of hCG, two groups were defined: low P (P < or = 0.9 ng/mL; conversion factor to SI unit, 3.180) and high P (P > 0.9 ng/mL). MAIN OUTCOME MEASURE(S): Blastulation (number of blastocysts/number of noncavitating embryos x 100) and pregnancy rates (PRs). RESULT(S): Blastulation rates were similar in the low and high P groups (51% and 48%, respectively). Moreover, patients included in the high P groups achieved significantly lower clinical and ongoing PRs (12% versus 29% and 7% versus 25%, respectively). CONCLUSION(S): The lack of difference in blastulation rates between the groups further supports the hypothesis that premature P elevation does not alter oocyte and embryo quality. Hence, the observed decrease in PRs is likely to reflect impaired endometrial receptivity in the high P group.

Adult↗