Biomedical subjects
Publications and source records attributed to R Fanchin.
Haemorrhagic interstitial pregnancies are commonly treated by cornual resection. This invasive procedure may increase the risk of uterine rupture in subsequent pregnancies. We report here a case of a haemorrhagic interstitial pregnancy, associated with a viable intrauterine pregnancy in a salpingectomized woman, which was treated successfully by curettage of the uterine cornu.
High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF-embryo transfer outcome. This prompted us to quantify prospectively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation, up to the time of blastocyst transfers, in 43 IVF-embryo transfer candidates. Contractility was assessed on the day of human chorionic gonadotrophin (HCG) administration, 4 days after HCG (non-cavitating embryo transfer; HCG + 4), and 7 days after HCG (blastocyst transfers; HCG + 7). For this, 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency. Our results indicated that a slight, yet significant, decrease in uterine contraction frequency, observed from the day of HCG (4.4 +/- 0.2 contractions/min) to HCG + 4 (3.5 + 0.2 contractions/min), was followed by a more pronounced, additional decrease between HCG + 4 and HCG + 7 (1.5 +/- 0.2 contractions/min; P < 0.001). In conclusion, during the luteal phase of ovarian stimulation, uterine contractility decreases progressively, and reaches a nearly quiescent status 7 days after HCG administration, at the time of blastocyst transfers. It is possible that such a uterine relaxation assists blastocyst implantation.
Recent renewed interest in uterine contractility stems from the possibility of directly visualizing uterine contractility on images generated by high-resolution ultrasound probes. During the menstrual cycle, three typical patterns of uterine contractility have been recognized. During the luteofollicular transition and early follicular phase (menses), the contractile event involves all layers of the myometrium and exerts antegrade (from fundus to cervix) expulsive forces. Characteristically, uterine contractions are often perceived by women at the time of menses, sometimes reaching the level of painful cramps (dysmenorrhea). In the late follicular phase, uterine contractility involves only the subendometrial layers of the myometrium and is never perceived by women. The primary function of uterine contractility in the late follicular phase is to facilitate the retrograde (cervix to fundus) transport of sperm towards the distal end of the fallopian tubes where fertilization normally takes place. Finally, the uterus reaches a stage of quiescence after ovulation (under the influence of progesterone) that characterizes the major part of the luteal phase. The present review summarizes our understanding of the physiological role of uterine contractility during the follicular phase and the possible implications in pathological circumstances such as endometriosis and dysmenorrhea.
The understanding and control of embryo implantation represents the major challenge for assisted reproductive technologies. Along with developments in basic research and efforts to optimize embryo quality, the improvement of noninvasive and reliable methods to assess uterine receptivity constitutes an important step toward meeting such a challenge. Today, ultrasound-based approaches to evaluate endometrial echogenicity and uterine perfusion and contractility are available for practical use. Increasing evidence indicates that echogenic patterns of the endometrium reflect histologic processes that are involved in the establishment of receptivity. This constitutes a possible explanation for the reported association between premature hyperechogenic patterns of the endometrium and poor implantation rates. Nevertheless, additional studies aiming at correlating further morpho-biochemical events in the endometrium with its echogenicity patterns are needed. Further, developments in vascular assessment by Doppler, Doppler-related, and vascular detection technologies will also be instrumental in monitoring and improving vascular changes that lead to uterine receptivity. Finally, data supporting the hypothesis that uterine contractility, as visualized by ultrasound, influences in vitro fertilization-embryo transfer (IVF-ET) pregnancy rates encourage further investigation on both the regulation and control of uterine contractions. This article discusses some of the advantages and limitations of ultrasonographic assessments of uterine receptivity in the perspective of the new millennium.
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In France, all embryos obtained after ovum donation have to be frozen. We present a brief background on this policy and expose our results, then discuss the rationale of such a policy in order to upgrade knowledge on the mechanism of vertical HIV transmission.
New GnRH antagonists are available in clinical practice. The different studies have confirmed the efficacy of these antagonists in preventing the LH surge. Two protocols have been described: in the multiple dose regimens, small doses of antagonist (0.25 mg) are injected starting on stimulation day 5 or 6 until hCG. In the single dose protocol, one injection of a larger dose (3 mg) is proposed in the late follicular phase. Local and general tolerance of the two compounds is very good. The results obtained with both regimens as compared with GnRH agonists in long protocols are showing a reduction in the stimulation length, in the consumption of gonadotrophins and in the incidence of the OHSS. The pregnancy rates are comparable in the good prognosis patients selected in the published studies. When the final tuning of these new protocols will be done, the advantages of GnRH antagonists in reducing the complications and side effects of ovarian stimulation will give to GnRH antagonists an important place in IVF.
OBJECTIVE: To determine whether endometrial echogenicity, assessed objectively by a computer-assisted system on the day of hCG administration, predicts endometrial receptivity in controlled ovarian hyperstimulation (COH) cycles for IVF-ET. DESIGN: Prospective analysis. SETTING: Assisted reproduction unit, Clamart, France. PATIENT(S): Two hundred twenty-one women (aged <38 years with a normal uterus and >/=2 grade A or B embryos transferred) undergoing 228 GnRH agonist and FSH/hCG cycles for IVF-ET. INTERVENTION(S): On the day of hCG administration, uterine ultrasound scans were digitized with an image analysis system. Endometrial echogenicity was assessed as the ratio of the extent of the hyperechogenic transformation over the whole endometrial thickness. According to this, cycles were sorted arbitrarily into six groups: <30% (n = 34), 31%-40% (n = 37), 41%-50% (n = 37), 51%-60% (n = 55), 61%-70% (n = 37), and >70% (n = 28). MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): The groups were similar in regard to population characteristics, ovarian response to COH, and embryology data. Pregnancy rates (59%, 57%, 35%, 20%, 16%, and 11%, respectively) and implantation rates (35%, 23%, 17%, 6%, 7%, and 3%, respectively) fell progressively and significantly from the low-echogenicity group to the high-echogenicity group. CONCLUSION(S): The present results confirm and extend previous observations that advanced hyperechogenic transformation of the endometrium is associated with poor IVF-ET outcome.
OBJECTIVE: To investigate the effects of hCG administered to patients undergoing controlled ovarian hyperstimulation on levels of ovarian hormones, including androgens. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Six infertile, normally ovulating volunteers. INTERVENTION(S): The women underwent controlled ovarian hyperstimulation with a GnRH agonist and hMG for IVF-ET. After the i.m. administration of hCG (10,000 IU), blood samples were drawn every 6 hours for 4 days. MAIN OUTCOME MEASURE(S): Plasma androstenedione, testosterone, progesterone, and E2 profiles. RESULT(S): Treatment with hMG increased plasma androstenedione and testosterone levels 1.4-fold and 2.6-fold, respectively. The administration of hCG did not increase plasma androstenedione and testosterone levels any further; mean daily levels remained at 2.3 ng/mL and 0.64 ng/mL, respectively. Circadian changes in androstenedione levels were evident after hCG administration. Plasma progesterone levels neared 10 ng/mL 19 hours after hCG administration, plateaued for 24 hours, and increased again thereafter. Plasma E2 levels declined during the first 2 days after hCG administration and then increased, concomitant with the second phase of progesterone elevation. CONCLUSION(S): In patients undergoing controlled ovarian hyperstimulation, androgen levels increased in response to hMG treatment, but no further elevation occurred after hCG administration. The rate of elevation of progesterone levels and the absolute levels achieved were 3-fold and 10-fold higher, respectively, than those observed during spontaneous menstrual cycles.
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.
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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.
OBJECTIVE: To synchronize the intercycle FSH elevation with exogenous E2 for programming ovulation in the menstrual cycle. DESIGN: Open single-arm study. SETTING: Teaching hospital. PATIENT(S): Twenty-six patients with infertility whose menstrual cycles normally lasted 25-35 days and who underwent our routine programming method for postcoital tests and ovulation evaluations. INTERVENTION(S): Participants received estradiol valerate (2 mg) twice a day from day 25 of the previous cycle until 1-15 days after the onset of menses. Women had ultrasonography on the last day of E2 treatment or on functional day 0 and 13 days later or on functional day 13. Hormones were determined on functional days 0, 3, 9, and 13. The increase in FSH in response to E2 withdrawal was defined as deltaFSH. MAIN OUTCOME MEASURE(S): LH surge and other ovulatory indices on functional day 13. RESULT(S): On functional day 13, 73% of the women had an LH surge. Fifteen percent had evidence of previous ovulation with low LH and elevated plasma P levels, and the remaining 12% had low LH levels and no evidence of past or imminent ovulation. Women with evidence of early ovulation were older and had higher FSH signal amplitude. CONCLUSION(S): It is feasible and practical to program ovulation in the menstrual cycle with exogenous E2. In 73% of women, the true duration of the follicular phase (intercycle FSH elevation to LH surge interval) remained constant (13 days). Hence, common fluctuations in menstrual cycle length mainly result from variations in the timing of the intercycle FSH elevation. Although rare, truly short follicular phases also exist (15%). This simple and practical system for programming natural ovulation offers new possibilities for using the menstrual cycle in assisted reproductive technology, at least in selected individuals.
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.
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.
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.
While the number of identified substances produced by the ovary increases steadily, it remains remarkable that the sole use of exogenous estrogen (E2) and progesterone (P) can prime optimal endometrial receptivity in women whose ovaries have failed or are absent. Early work showed that a marked leeway existed in the acceptable duration of the E2-only phase of endometrial priming. Subsequently, a sequence of transformations are induced by exogenous progesterone that reproduces classical findings made in the menstrual cycle. Secretory changes in endometrial glands are best seen between the 4th and 6th day of progesterone administration (day 18-20 of an ideal cycle where progesterone exposure starts on day 15). Predecidual changes of the endometrial stroma are apparent starting on the 10th day of progesterone exposure (day 24). Contrary to earlier belief, even maximal alterations in the plasma E2 to progesterone ratio fails to alter the endometrial morphology of either glands or stroma. More recently it has been recognized that E2 and progesterone also affect uterine contractility. It has been postulated that excessively high levels of E2 may increase uterine contractility and adversely affect implantation rates in in-vitro fertilization (IVF). Exogenous progesterone has been shown to exert utero-relaxing effects and it has been hypothesised that progesterone supplementation before embryo transfer (ET) may improve receptivity in IVF.
We have previously observed that exogenous oestradiol can delay the intercycle increase in plasma follicle stimulating hormone (FSH). The increase in plasma FSH that follows discontinuation of exogenous oestradiol peaks after 3 days. We have now studied the possibility of using exogenous oestradiol to synchronize the increase in endogenous FSH with the onset of human menopausal gonadotrophin (HMG) treatment in controlled ovarian hyperstimulation (COH). A total of 30 women aged 35.1+/-6.3 years (mean+/-SD) undergoing ovarian stimulation received 2 mg of oestradiol valerate twice daily starting on day 25 of the previous menstrual cycle until the first Tuesday following menses. Ovarian stimulation was initiated 3 days later. On the last day of oestradiol treatment, plasma oestradiol, FSH and luteinizing hormone (LH) (mean+/-SEM) were 566+/-53 (pmol/l), 3.8+/-0.4 (IU/l) and 5.5+/-0.8 (IU/l) respectively. After 3 days, the FSH and LH (mean+/-SEM) had increased to 6.7+/-0.7 and 6.9+/-0.7 (IU/l) respectively while oestradiol decreased to 251+/-29 (pmol/l). The mean number (+/-SEM) of HMG ampoules used was 25.1+/-2.7 and treatment lasted 11.3+/-0.9 days. Five women became pregnant for a pregnancy rate (ongoing) of 19 (15)%. If all women aged >40 years (six women who did not become pregnant) were excluded from analysis the pregnancy rate (ongoing) was 24 (19%). These results indicate that exogenous oestradiol can safely be used for the synchronization of endogenous and exogenous FSH stimuli in COH. This approach provides the practical advantage of permitting an advanced timing of the onset of COH treatments when gonadotrophin-releasing hormone (GnRH) agonists are not used, which improves treatment convenience for patients and team members alike. Further development of this model may enable control of the onset of natural cycles which may find practical applications for timing assisted reproductive techniques (intrauterine insemination or in-vitro fertilization) in the natural cycle.