Early follicle development alters the relationship between antral follicle counts and inhibin B and follicle-stimulating hormone levels on cycle day 3.

OBJECTIVE: To verify whether, during the luteal-follicular transition, increased inhibin B production by abnormally large follicles modifies the expected relationship between the number of follicles and peripheral inhibin B and FSH levels. DESIGN: Prospective study. SETTING: Teaching hospital, France. PATIENT(S): A total of 192 normo-ovulatory women. INTERVENTION(S): Serum inhibin B and FSH levels and numbers and sizes of antral follicles (3-12 mm) were measured on cycle day 3. MAIN OUTCOME MEASURE(S): The strength of hormonal-follicular correlations was assessed in two groups formed according to the presence (large follicle group; n = 73) or absence (small follicle group; n = 119) of one follicle measuring >7 mm. RESULT(S): Serum inhibin B and FSH levels were correlated with antral follicle counts (r = 0.32 and r = -0.44, respectively). These relationships were significantly weaker in the large follicle group (r = 0.24 and r = -0.28, respectively) than in the small follicle group (r = 0.51 and r = -0.55, respectively). CONCLUSION(S): Antral follicle size influences serum inhibin B and FSH levels and alters their expected relationship with the number of antral follicles on day 3. These results contribute to clarifying the controversial role of serum inhibin B and FSH levels in the prediction of ovarian follicular status.

Impact of early cleaved zygote morphology on embryo development and in vitro fertilization-embryo transfer outcome: a prospective study.

OBJECTIVE: To evaluate the impact of the first division morphology on embryo development and IVF-embryo transfer outcome. DESIGN: Prospective study. SETTING: Teaching hospital, France. PATIENT(S): All zygotes from 201 couples were checked for early cleavage. We defined as "even," early cleaved (EC) zygotes with 2 cells of even size; as "uneven," EC zygotes with 2 cells of uneven size; and as "fragmented," EC zygotes with more than 20% fragmentation rate. Day 2 embryo quality was assessed as "top" embryo or "non-top," with the evaluation of multinucleated blastomeres. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Day 2 embryo quality, pregnancy and implantation rates. RESULT(S): Among EC zygotes, 59.1% were even, 13.0% were uneven, and 27.9% were fragmented. Even EC yielded more "top" embryos and less multinucleated blastomere embryos than uneven EC (77.0% vs. 46.3%) and fragmented EC (77.0% vs. 13.9%). The 125 double embryo transfers that comprised at least one embryo derived from even EC zygote led to higher pregnancy rate (PR) (64.0% vs. 43.4%) and implantation rate (42.0% vs. 27.6%) compared to the 76 double embryo transfers with embryos derived from breakdown or 2PN zygotes. CONCLUSION(S): The morphology of the early cleaved zygote is involved in embryo development. Evaluation of this morphology is an effective and valuable method of assessing the embryo quality.

Five years' experience of preimplantation genetic diagnosis in the Parisian Center: outcome of the first 441 started cycles.

OBJECTIVE: To investigate the evolution of techniques and strategies and to evaluate the results of preimplantation genetic diagnosis (PGD) from January 2000 to December 2004 in chromosomal, monogenic and mitochondrial DNA disorders treated at our institution. DESIGN: Retrospective study. SETTING: Single French Parisian PGD center. PATIENT(S): Patients at risk of transmitting a serious genetic disorder to their offspring. INTERVENTION(S): 171 couples enrolled in the program undergoing stimulated and frozen embryo replacement cycles with PGD. MAIN OUTCOME MEASURE(S): Results of the 441 first PGD cycles performed for various genetic conditions. RESULT(S): During 5 years, 416 stimulation and 25 frozen embryo replacement cycles were started, among which 52 clinical and 47 ongoing pregnancies occurred. In stimulation cycles, the overall ongoing pregnancy rate was 24% per embryo transfer, 11% per started cycle, and 27% per couple. The implantation rate was 16%. CONCLUSION(S): These encouraging results demonstrate that PGD might be considered as a valid alternative to prenatal diagnosis. Nevertheless, couples referred for PGD must be selected and counseled appropriately, considering the complexity of the treatment and the relatively low take-home baby rate.

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.

[Preimplantation genetic diagnosis]. / Le diagnostic préimplantatoire.

Preimplantation genetic diagnosis (PGD) purpose is to assess the genetic status of 3 day-old embryos. Thus, PGD offers to couples "at-risk" of transmitting a genetic disorder an earlier option to prenatal diagnosis. The first successful PGD was reported in 1990 but in France, PGD has been authorized only since 2000. Worldwide, 7,000 PGD have been performed, leading to the birth of more than one hundred unaffected children. New applications are introduced regularly and the number of diagnoses available is increasing at a rapid rate. In France the practice of PGD is strictly supervised by the bioethical law. However, indications vary considerably in countries where the absence of law authorizes all the practices, raising sometimes serious ethical issues.

Optimising the semi natural cycle IVF: the importance of follicular flushing.

To evaluate the importance of follicular flushing on semi natural cycles IVF, we have compared prospectively the reproductive potential of oocytes obtained from follicular fluid (group A, n = 79) to those obtained from follicular flushing (group B, n = 47) in 146 oocyte pick-ups. The groups A and B were similar on the fertilisation rate (79.7% versus 88.1%, respectively), percentage of superior grade embryos (28.8% versus 37.8%) and the implantation rate (24.1% versus 44.1%) and 53.6% of total clinical pregnancies were obtained from group B. The practice of follicular flushing on IVF semi natural cycle improves the pregnancy rate. The oocytes obtained by follicular flushing had the same reproductive potential than those obtained on follicular fluid.

[Prenatal and preimplantation genetic diagnosis: decision tree, new practices?]. / Diagnostic prénatal et diagnostic pré-implantatoire: arbre décisionnel, nouvelles pratiques?

Preimplantation genetic diagnosis (PGD) purpose is to assess the genetic status of 3 day-old embryos. PGD offers thus to couples "at-risk" of a genetic disorder an earlier option to prenatal diagnosis (PND). At the beginning, PGD's indications, patients and law were very closed to PND, but PGD specificities are gradually raising. Particularly, indications vary considerably in countries where the absence of law authorizes all the practices. Some of these applications are moreover raising serious ethical issues. Even in France, where this activity is particularly supervised, the recent modification to the law marks this evolution.

Frozen section examination of the endocervical margin of cervical conization specimens.

OBJECTIVE: We conducted this retrospective study to determine accuracy of frozen section examination of endocervical margin during cold knife conization. METHODS: Between June 1993 and June 2001, 310 consecutive patients underwent cervical conization for squamous intraepithelial lesion or stage IA1 cervical cancer. Before 1997, the surgical specimens of 149 patients were processed following a standard pathological procedure (historical group). After 1997, a frozen section of the upper endocervical margin was processed during surgery for 161 patients. If the upper endocervical margin was involved with intraepithelial neoplasia, the surgeon performed a second resection if possible. Results of the frozen section examination were compared with the final diagnoses to determine sensitivity, specificity, and positive and negative predictive values. The usefulness of this procedure was evaluated by comparison of positive margin status rate with the one of the historical control group. RESULTS: For the diagnosis of intraepithelial neoplasia involving the endocervical margin, the sensitivity, specificity, and positive and negative predictive values of frozen section were 91%, 100%, 100%, and 98%, respectively. Eleven patients had definitive positive endocervical margin in the frozen section group (three false negatives, six patients without additional resection, and two patients with intraepithelial neoplasia involving the upper margin of the additional resection) and 17 patients in the historical group (P =.16). CONCLUSION: Frozen section examination of the endocervical margin of cervical specimen obtained during cold knife conization is highly accurate. Its clinical relevance has to be demonstrated in a multicenter study.