Hysteroscopy in women with implantation failures after in vitro fertilization: findings and effect on subsequent pregnancy rates.

OBJECTIVE: To evaluate hysteroscopic findings and estimate the effect of hysteroscopy on achieving a pregnancy in women with a history of 2 implantation failures after in vitro fertilization (IVF). DESIGN: Prospective observational and matched case control study. DESIGN CLASSIFICATION: II-2. SETTING: Private assisted reproduction units. PATIENTS: A total of 1475 patients with a history of 2 consecutive implantation failures after IVF who had a hysteroscopy were studied; there were 414 matched pairs of women with a similar history who either had or did not have a hysteroscopy. INTERVENTIONS: Hysteroscopy (diagnostic or operative), IVF/intracytoplasmic sperm injection cycle. MEASUREMENTS AND MAIN RESULTS: Hysteroscopic findings, clinical pregnancy rate (CPR), and ongoing pregnancy rate (OPR) were measured. In all, 36.6% of the study population had abnormal hysteroscopic findings and 22.2% had unsuspected findings; women with abnormal hysteroscopic findings showed significantly increased CPR and increased OPR in a new IVF cycle compared with those with a normal hysteroscopy result. Women who had a hysteroscopy showed significantly increased CPR and OPR compared with matched control subjects who did not have the procedure. Hysteroscopy and appropriate therapy significantly increased the chances of achieving a subsequent clinical and ongoing pregnancy. CONCLUSION: Women with 2 implantation failures after IVF had a remarkably high possibility for unsuspected abnormalities seen at hysteroscopy. Hysteroscopy could serve as a positive prognostic factor for achieving a subsequent pregnancy.

Retrotransposon RNA expression and evidence for retrotransposition events in human oocytes.

Although human diseases of retrotransposition-derived etiology have been documented, retrotransposon RNA expression and the occurrence of retrotransposition events in the human oocyte are not studied. We investigated the RNA expression of L1 and HERV-K10 retrotransposons in human oocytes by RT-PCR analysis with designed primers. Using denucleated germinal vesicles (GVs), we detected RT-PCR products of expressed L1, HERV-K10 and, unexpectedly, SINE-R, VNTR and Alu (SVA) retrotransposons. Their transcript specificities were identified as such following RNA-FISH and their origin by cloning and sequence alignment analyses. Assessing the expression level in comparison with somatic cells by densitometry analysis, we found that although in normal lymphocytes and transformed HeLa cells their profile was in an order of L1 > HERV-K10 > SVA, remarkably this was reversed in oocytes. To investigate whether de novo retrotransposition events occur and reverse transcriptases are expressed in the human oocyte, we introduced in GVs either a retrotransposition active human L1 or mouse reverse transcriptase deficient-VL30 retrotransposon tagged with an EGFP-based retrotransposition cassette. Interestingly, in both the cases, we observed EGFP-positive oocytes, associated with an abnormal morphology for L1 and granulation for VL30, and the retrotransposition events were confirmed by PCR. Our results: (i) show that L1, HERV-K10 and SVA retrotransposons are transcriptionally expressed and (ii) provide evidence, for the first time, for retrotransposition events occurring in the human oocyte. These findings suggest that both, network of retrotransposon transcripts and controlled retrotranspositions, might serve important functions required for oocyte development and fertilization while the uncontrolled ones might explain the onset of genetic disorders.

Comparison of embryo transfer on day 2, day 3, and day 6: a prospective randomized study.

A prospective randomized study of 243 embryo transfers revealed that the use of blastocysts in assisted reproductive technology is not more effective than the use of day 2 and day 3 embryos.