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Renato Fanchin

Publications and source records attributed to Renato Fanchin.

At least 19 recordsLinked to original sources

The 3D vascular status of the follicle after HCG administration is qualitatively rather than quantitatively associated with its reproductive competence.

BACKGROUND: The objective of this study was to determine whether the vascular status of a single pre-ovulatory follicle is associated quantitatively and/or qualitatively with its reproductive competence. METHODS: We studied 61 monofollicular IVF-embryo transfer cycles. Just before single oocyte retrieval, follicle vascularization was detected by transvaginal power-Doppler, 3-dimensionally reconstructed, and analysed quantitatively by coloured/gray voxel ratio [vascularization index (VI)] and qualitatively by blood cell displacement [flow index (FI)] calculation. Cycles were sorted in two sets of two groups: low VI ( 8%, n = 17); low FI ( 30, n = 39). RESULTS: Patients' characteristics, fertilization rates, and embryo morphology were comparable in all groups. In contrast, clinical pregnancy rates/oocyte retrieval (4% versus 33%, P < 0.009) and implantation rates (11% versus 50%, P < 0.04) were markedly poorer in the low as compared to the high FI groups, respectively, but remained similar between the low and the high VI groups (22% versus 23% and 38% versus 44%, respectively). CONCLUSIONS: A qualitative (FI) rather than quantitative (VI) relationship exists between vascular status and functional quality of the follicle after HCG administration.

Adult↗

Anti-Müllerian hormone: clinical insights into a promising biomarker of ovarian follicular status.

In contrast to most hormonal biomarkers of the follicular status, anti-Müllerian hormone (AMH) is exclusively produced by the granulosa cells of a wide range of follicles (primary to the early antral stages), presumably FSH-independently and with little susceptibility to disorders of antral follicle growth during the luteal-follicular transition. This paper summarizes the authors' clinical research on the role of AMH as a marker of ovarian functioning. It shows that the relationship between antral follicle counts and serum AMH concentrations is stronger than that observed with FSH, inhibin B and oestradiol on day 3, and that intercycle reproducibility of AMH measurements is better than the latter parameters. In addition, peripheral AMH concentrations decline during ovarian stimulation, thus confirming that maturing follicles loose progressively their ability to produce AMH. Indeed, follicular fluid (FF) AMH concentrations in small antral follicles are 3-fold as high as AMH in pre-ovulatory follicles. Further, human chorionic gonadotrophin-driven luteinization additionally curtails follicular AMH production. Finally, AMH production measured in FF from individual follicles is increased in women having normal follicular counts and responsiveness to ovarian stimulation. Together, these data reinforce the soundness of AMH measurements as a quantitative and possibly qualitative marker of granulosa cell activity and health.

Anti-Mullerian Hormone↗

High reproducibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status.

BACKGROUND: Our aim was to compare the intercycle reproducibility of serum anti-Mullerian hormone (AMH) measurements with that of other markers of ovarian follicular status. METHODS: Forty-seven normo-ovulatory, infertile women underwent serum AMH, inhibin B, estradiol and FSH measurements and early antral follicle (2-12 mm in diameter) counts by transvaginal ultrasound on cycle day 3 during three consecutive menstrual cycles. Reproducibility of measurements was estimated using intra-class correlation coefficient (ICC) calculation. We also assessed the number of replicate measurements theoretically needed to reach satisfactory reliability of results. RESULTS: Serum AMH showed significantly higher reproducibility (ICC, 0.89; 95% confidence interval, 0.83-0.94) than inhibin B (0.76; 0.66-0.86; P < 0.03), estradiol (0.22; 0.03-0.41; P < 0.0001) and FSH levels (0.55; 0.39-0.71; P < 0.01), and early antral follicle counts (0.73; 0.62-0.84; P < 0.001), and reached satisfactory reliability with a single measurement. CONCLUSIONS: The improved cycle-to-cycle consistency of AMH as compared with other markers of ovarian follicular status is in keeping with its peculiar production by follicles at several developmental stages and further supports its role as a cost-effective, reliable marker of ovarian fertility potential.

Adult↗

Per-follicle measurements indicate that anti-müllerian hormone secretion is modulated by the extent of follicular development and luteinization and may reflect qualitatively the ovarian follicular status.

OBJECTIVE: To investigate the possible influence of follicular maturation and luteinization on anti-müllerian hormone (AMH) secretion and the relationship between per-follicle AMH levels, ovarian follicular status, and responsiveness to controlled ovarian hyperstimulation (COH). DESIGN: Prospective study. SETTING: University hospital in France. PATIENT(S): Thirty seven in vitro fertilization/embryo transfer candidates undergoing COH. INTERVENTION(S): On the day of oocyte retrieval, serum samples and follicular fluids from two small (8-12 mm in diameter) and two large (16-20 mm in diameter) follicles were collected for AMH, E2, and progesterone (P4) measurements. MAIN OUTCOME MEASURE(S): Per-follicle AMH levels. RESULT(S): Small follicles secreted AMH levels that were approximately three times as high as large follicles. Follicular fluid AMH and P4 levels were negatively correlated to each other both in small and large follicles. Per-follicle AMH levels in both follicular classes were positively correlated with antral follicle count on cycle day 3 before COH and with growing follicle (> or =12 mm) count and oocytes retrieved, but negatively correlated with FSH requirement. CONCLUSION(S): Both final follicular maturation and luteinization interfere with granulosa cell AMH production. The relationship between intrafollicular AMH content, the surrounding follicular status, and ovarian response to COH indicates that peripheral AMH levels reflect not only follicle count but also per-follicle AMH production.

Adult↗

In vitro fertilization and embryo transfer in seminatural cycles for patients with ovarian aging.

OBJECTIVE: To investigate whether seminatural cycle is a reasonable management for ovarian aging patients. DESIGN: Prospective study. SETTING: ART Unit, Clamart, France. PATIENT(S): Seventy-five women, 158 cycles. INTERVENTION(S): Infertile women who presented with ovarian aging (defined as low ovarian reserve and characterized by cycle day 3 high FSH, high E2, and/or low inhibin B and/or previous cycle cancellations due to poor ovarian response to COH) were studied. Patients were offered up to three cycles. Treatment was scheduled as follows. From cycle day 8 onward the selection of the dominant follicle was monitored by ultrasound and hormonal measurements. When the dominant follicle appeared, patients received GnRH antagonist and, thereafter, hMG to support further follicular development. MAIN OUTCOME MEASURE(S): Implantation rate and clinical pregnancy. RESULT(S): Twenty-eight of 158 cycles were cancelled (17.7%). Oocyte pickups were performed in 119 (75.3%) cycles, 91 (57.6%) mature oocytes were retrieved, and 67 (42.4%) embryos transferred. Nineteen clinical pregnancies were obtained; the cumulative pregnancy rate per patient, after 3 cycles, was 35.2%. CONCLUSION(S): Use of a seminatural cycle is a reasonable management for patients with ovarian aging who have ovulatory menstrual cycles. It achieves a high implantation rate (28.3%).

Adult↗

Hormonal manipulations in the luteal phase to coordinate subsequent antral follicle growth during ovarian stimulation.

During the early follicular phase in the menstrual cycle, antral follicle sizes are often markedly heterogeneous. These follicular size discrepancies may, at least in part, result from the early exposure of FSH-sensitive follicles to gradient FSH concentrations during the preceding luteal phase. In addition, they potentially affect the results of ovarian stimulation. Indeed, pre-existing follicle size discrepancies may encumber coordinated follicular growth during ovarian stimulation, thereby reducing the number of follicles that reach maturation at once. To investigate this issue, three clinical studies were conducted to test the hypothesis that luteal FSH suppression could coordinate follicular growth. First, luteal FSH concentrations were artificially lowered by administering physiological oestradiol doses and measured follicular characteristics on the subsequent day 3. Second, it was verified whether luteal oestradiol administration could promote the coordination of follicular growth during ovarian stimulation and improve its results. Third, the effects of premenstrual gonadotrophin-releasing hormone (GnRH) antagonist administration on follicular characteristics were assessed during the early follicular phase. The results showed that luteal FSH suppression by either oestradiol or GnRH antagonist administration reduces the size and improves the homogeneity of early antral follicles during the early follicular phase, an effect that persists during ovarian stimulation. Coordination of follicular development may optimize ovarian response to short GnRH agonist and antagonist protocols, and constitutes an attractive approach to improving their outcome.

Adult↗

Coordination of antral follicle growth: basis for innovative concepts of controlled ovarian hyperstimulation.

Among the key objectives of controlled ovarian hyperstimulation (COH) is the achievement of adequate coordination of multiple follicular growth to trigger ovulation when most of follicles have reached concomitant maturation. However, during the early follicular phase, early antral follicles present noticeable size heterogeneities that may be amplified during COH. To challenge the hypothesis that this phenomenon results, at least in part, from the early exposure of antral follicles to gradient follicle-stimulating hormone (FSH) levels during the preceding late luteal phase, we conducted three clinical studies. First, we artificially lowered luteal FSH levels by administering estradiol (E (2)) and measured follicular characteristics on the subsequent day 3. Second, we verified whether luteal E (2) administration could promote the coordination of follicular growth during COH and improve its results. Third, we assessed the effects of premenstrual gonadotropin-releasing hormone (GnRH) antagonist administration on follicular characteristics during the early follicular phase. Our results showed that luteal FSH suppression by either E (2) or GnRH antagonist administration reduces the size and improves the homogeneity of early antral follicles during the early follicular phase, an effect that persists during COH. Coordination of follicular development may optimize ovarian response to short GnRH agonist and antagonist protocols, and constitutes an attractive approach to improving their outcome.

Adult↗

The chemokine SDF-1/CXCL12 contributes to T lymphocyte recruitment in human pre-ovulatory follicles and coordinates with lymphocytes to increase granulosa cell survival and embryo quality.

We investigated the production and the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in pre-ovulatory follicles of women undergoing in vitro fertilization. We detected CXCL12 and its receptor CXCR4 by flow cytometry, western blotting and RT-PCR. We tested cell migration in Transwell experiments. We measured apoptosis using delta psi m-sensitive fluorescent probe DiOC6(3) and we screened apoptosis-related gene expression with macro-arrays. Granulosa cells from follicular aspirates produce CXCL12 that contributes to T lymphocytes recruitment. CXCL12 reduces early apoptosis of granulosa cells. This effect is accompanied by a shift of bcl2/bax ratio, and decreased expression of p53-targeted genes (pig7, pig8, p21, gadd45). Removal of lymphocytes disables CXCL12-mediated anti-apoptotic effect on granulosa cells. Anti-apoptotic activity of CXCL12 is positively correlated to high quality of embryos. In conclusion, CXCL12 is locally produced by luteinizing granulosa cells. It specifically contributes to T lymphocytes recruitment and coordinates with local lymphocytes to increase granulosa cell survival and embryo quality.

Adult↗

Dynamics of serum anti-Müllerian hormone levels during the luteal phase of controlled ovarian hyperstimulation.

BACKGROUND: To investigate the dynamics of serum anti-Müllerian hormone (AMH) levels during the luteal phase of controlled ovarian hyperstimulation (COH) and its possible association with follicle development. METHODS: We prospectively studied 34 women undergoing COH with GnRH agonist and FSH. On the day of hCG (dhCG), serum AMH, estradiol (E2), progesterone and hCG levels were measured, and ovarian follicles were sorted into three size classes: <12, 12-15 and 16-22 mm. Hormonal measurements were repeated 4 days (hCG + 4) and 7 days (hCG + 7) after hCG. RESULTS: From dhCG to hCG + 4, we observed a decline in serum AMH levels (-64 +/- 3%; P < 0.0001), which paralleled that of E2 levels. From hCG + 4 to hCG + 7, an increase in AMH levels occurred (82 +/- 28%; P < 0.02), whose magnitude was correlated with the number of < 12 mm follicles (r = 0.68; P < 0.0001) but not with other follicle size classes nor with the remaining hormone levels. CONCLUSIONS: After hCG, AMH levels initially decline, presumably as an effect of follicle luteinization, then increase during the mid-luteal phase. Although the mechanisms implicated in the mid-luteal AMH increase are unclear, its positive association with small follicle count, but not with luteal progesterone and E2 levels, supports the hypothesis that AMH levels might reflect luteal follicle development.

Adult↗

Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation.

OBJECTIVE: To investigate whether premenstrual administration of a GnRH antagonist coordinates early antral follicle sizes during the subsequent follicular phase. DESIGN: Prospective, longitudinal study. SETTING: University Hospital in France PATIENT(S): Twenty-five women, 50 cycles. INTERVENTION(S): On cycle day 2 (control/day 2), women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. On day 25, they received a single cetrorelix acetate administration, 3 mg. On the subsequent day 2 (premenstrual GnRH antagonist/day 2), participants were re-evaluated as on control/day 2. MAIN OUTCOME MEASURE(S): Magnitude of follicular size discrepancies. RESULT(S): Follicular diameters (4.1 +/- 0.9 vs. 5.5 +/- 1.0 mm) and follicle-to-follicle size differences decreased on premenstrual GnRH antagonist/day 2 as compared with control/day 2. Consistently, FSH (4.5 +/- 1.9 vs. 6.7 +/- 2.4 mIU/mL), E(2) (23 +/- 13 vs. 46 +/- 26 pg/mL), and inhibin B (52 +/- 30 vs. 76 +/- 33 pg/mL) were lower on GnRH antagonist/day 2 than on control/day 2. CONCLUSION(S): Premenstrual GnRH antagonist administration reduces diameters and size disparities of early antral follicles on day 2, likely through the prevention of luteal FSH elevation and early follicular development. This simple, original approach may be used to coordinate multifollicular development in controlled ovarian hyperstimulation.

Adult↗

Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens.

OBJECTIVE: To investigate whether luteal E(2) administration reduces size discrepancies of early antral follicles. DESIGN: Prospective, crossover study. SETTING: ART unit, Clamart, France. PATIENT(S): Sixty women and 120 cycles. INTERVENTION(S): On cycle day 3 (baseline day 3), all women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. From day 20 until the next cycle day 2, 30 of them received oral 17beta-E(2), whereas the remaining women served as controls. The day after E(2) discontinuation (E(2) day 3) or on subsequent cycle day 3 (control day 3), participants were reevaluated as on baseline day 3. MAIN OUTCOME MEASURE(S): Magnitude of follicular size discrepancies. RESULT(S): Follicular size discrepancies and follicular diameters were significantly attenuated on E(2) day 3 (3.7 +/- 0.5 mm) as compared with baseline day 3 (4.9 +/- 1.0 mm), but not in controls (5.0 +/- 0.8 vs. 4.9 +/- 0.8 mm). FSH (4.3 +/- 1.9 vs. 7.3 +/- 3.3 mIU/mL) and inhibin B (34 +/- 28 vs. 71 +/- 32 pg/mL) levels were consistently lower on E(2) day 3 than on baseline day 3 but remained unchanged in controls. CONCLUSION(S): Luteal E(2) administration reduces the size and improves the homogeneity of early antral follicles on day 3. This approach may be instrumental in synchronizing follicular development during controlled ovarian hyperstimulation.

Adult↗

Luteal estradiol administration strengthens the relationship between day 3 follicle-stimulating hormone and inhibin B levels and ovarian follicular status.

OBJECTIVE: To investigate whether the prevention of early follicular growth by luteal E(2) administration improves the relationship between day 3 hormone measurements and the ovarian follicular status. DESIGN: Prospective, cohort study. SETTING: Assisted reproductive technology unit in Clamart, France. PATIENT(S): One hundred sixty-two infertile women. INTERVENTION(S): Participants received oral 17beta-E(2), 4 mg/day, from day 20 to the next cycle day 1 (n = 81) or served as controls (n = 81). Serum E(2), inhibin B, and FSH were measured during the 3 days after E(2) discontinuation (FD1, FD2, and FD3) in E(2)-treated women and on cycle day 3 (CD3) in controls. Early antral follicles were counted at ultrasound scans on FD3 and CD3. MAIN OUTCOME MEASURE(S): Hormonal-follicular correlations on FD3 and CD3. RESULT(S): As expected, after E(2) withdrawal, inhibin B and FSH increased from FD1 to FD3 whereas E(2) decreased. Correlations between FSH and inhibin B and follicular counts were stronger on FD3 than on CD3. CONCLUSION(S): Luteal E(2) administration notably strengthens the relationship between serum FSH and inhibin B levels and the number of antral follicles on day 3. This approach may represent an alternative test of ovarian follicular status.

Adult↗

Comparison of changes in uterine contraction frequency after ovulation in the menstrual cycle and in in vitro fertilization cycles.

OBJECTIVE: To compare changes in uterine contraction (UC) frequency occurring after ovulation in the menstrual cycle and in IVF and to clarify UC anomalies encountered in IVF. DESIGN: Prospective crossover trial. SETTING: University infertility clinic. PATIENT(S): Six women seeking IVF for male factor infertility having regular menstrual cycles were studied during the menstrual cycle and IVF. INTERVENTION(S): Identification of LH surge in the menstrual cycle. Measurement of plasma E(2) and P levels and assessment of UC frequency by direct ultrasound visualization on the day of LH surge in the menstrual cycle and the day of hCG administration in IVF and every 2 days thereafter for 6 days. MAIN OUTCOME MEASURE(S): Uterine contraction (UC) frequency and plasma E(2) and P levels. RESULT(S): UC frequency was similar on the day of LH surge (5/minute) and hCG administration (5.3/minute). Establishment of uteroquiescence was more prompt in the menstrual cycle than in IVF, with lower UC frequency 4 days after LH surge compared with 4 days after hCG, while E(2) and P levels were higher in IVF. Six days after LH surge/hCG administration, UC frequency was low in the menstrual cycle and in IVF. CONCLUSION(S): High UC frequency in IVF at the time of ET results from delayed establishment of uteroquiescence after ovulation in IVF as compared with the menstrual cycle. In IVF, low UC frequency 6 days after hCG may contribute to the higher pregnancy rates observed with blastocyst transfers.

Adult↗

Premature LH and progesterone rise in intrauterine insemination cycles: analysis of related factors.

Premature LH and progesterone surges are associated with different factors and hormonal modulators. The aim of the present study was (i) to investigate the clinical and laboratory factors and (ii) to highlight the importance of different stimulation protocols in associated premature LH and progesterone surges in intrauterine insemination (IUI) cycles. The study involved a retrospective investigation of 75 patients undergoing IUI for infertility treatment (135 IUI cycles) between 1996 and 2000, with initial serum LH concentrations >10 mIU/ml during ovarian stimulation. Ultrasound characteristics, follicular sizes, serum oestradiol, progesterone and LH concentrations and ovarian stimulation protocols were measured. There was a wide range of oestradiol serum concentrations (93-2245 pg/ml) and follicular size (12-25 mm). In 49.6% of cycles, the dominant follicle was <16.5 mm. Patients with >2 follicles measuring <15 mm had higher oestradiol serum concentrations (P = 0.008). Multiple regression analyses revealed no association between these variables and premature LH/progesterone surge. In conclusion, LH/progesterone surges cannot be predicted utilizing clinical parameters normally employed, e.g. ultrasound serum oestradiol assay or ovarian stimulation protocol. Patients with follicles >14 mm or more and with high numbers of small follicles and high oestradiol are at risk of a spontaneous LH surge. These variables can be used to time the administration of GnRH antagonist administration until better predictive factors are demonstrated.

Adult↗

Clinical and laboratory evaluation of hospitalized patients with severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an important complication of ovarian stimulation and IVF that enhances patients' morbidity. To evaluate any increased incidence of hospitalization from severe OHSS during 2000, this study analysed certain clinical, ultrasound and laboratory characteristics of hospitalized patients with severe OHSS. These studies were carried out on women undergoing IVF who were hospitalized because of severe OHSS between 1996 and 2000 at the Hôpital Antoine Béclère. Patients' ages and serum hormone concentrations were collected on day 3 of ovarian stimulation for various assays, and laboratory and ultrasound measurements taken during ovarian stimulation for IVF were compared. An increase was noted during last year in the frequency of the severe form of OHSS requiring hospitalization (0.9 versus 1.8%, P < 0.05). Patients' ages and hormonal characteristics on day 3 of menstrual cycle, and laboratory and ultrasound variables were similar between the two groups. In addition, the increased incidence of OHSS during 2000 was not associated with any special laboratory or ultrasound parameter, and the policy of ovarian induction had not changed. It is essential to introduce a simple ovarian stimulation protocol providing acceptable IVF results with a minimum of risk.

Adult↗

Confronting the hidden face of progesterone during the follicular phase.

Sporadic cases of late follicular phase progesterone elevation have been described in ART cycles despite routine blockage of endogenous gonadotropins with GnRH agonists, the mechanism of which has been eluding our scrutiny. In this issue of JARG, Levran et al. report the first cases of adult-onset mild form of congenital adrenal hyperplasia (CAH) linked to a deficit in 17-hydorixyloase (17-OH ase). Contrary to CAH due to deficit 21-OH ase, these not only affect the adrenals but also the FSH driven production of E2 and androgen by the ovary thereby leading to progesterone "accumulation" during the follicular phase. Levran's findings offer new hypotheses for explaining the cases late follicular progesterone elevation particularly, when encountered in COH cycles associated with poor E2 elevation. And more importantly, Levran's findings offer new possible options for minimizing their consequences on ART outcome.

Adrenal Hyperplasia, Congenital↗

Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3.

BACKGROUND: The study aim was to compare the relationship between serum anti-Müllerian hormone (AMH) levels and other markers of ovarian function with early antral follicle count on day 3. METHODS: A total of 75 infertile women was studied prospectively. On cycle day 3, serum levels of AMH, inhibin B, estradiol (E(2)), FSH and LH levels were measured, and the number of early antral follicles (2-10 mm in diameter) estimated at ultrasound scanning to compare the strengths of hormonal-follicular correlations. RESULTS: Median (range) serum levels of AMH, inhibin B, E(2), FSH and LH were 1.39 ng/ml (0.24-6.40), 90 (16-182) pg/ml, 31 (15-111) pg/ml, 7.0 (2.9-19.3) mIU/ml and 4.7 (1.2-11.7) mIU/ml respectively, and follicular count was 12 (1-35). Serum AMH levels were more strongly correlated (P < 0.001) with follicular count (r = 0.74, P < 0.0001) than were serum levels of inhibin B (r = 0.29, P < 0.001), E(2) (r = -0.08, P = NS), FSH (r = -0.29, P < 0.001) and LH (r = 0.05, P = NS). CONCLUSIONS: Serum AMH levels were more robustly correlated with the number of early antral follicles than inhibin B, E(2), FSH and LH on cycle day 3. This suggests that AMH may reflect ovarian follicular status better than the usual hormone markers.

Adult↗