FEMALE INFERTILITY: Embryology and Genetics

Hum Reprod 2001 Aug;16(8):1714-8
Morphology of in-vitro matured oocytes: impact on fertility potential and embryo quality. Mikkelsen AL, Lindenberg S.
The Fertility Clinic Herlev University Hospital, Fruebjergvej 3, DK-2100 Copenhagen, Denmark. alm@ciconia.dk
BACKGROUND: The purpose of the present study was to investigate the morphology of in-vitro matured metaphase II (MII) oocytes and to observe if there was a difference in the morphology between polycystic and normal ovaries. Furthermore, the morphology of in-vitro matured MII oocytes was related to their subsequent fertilization and cleavage rates and to embryo quality. METHODS: This retrospective study included 264 MII oocytes obtained in 100 consecutive cycles. Oocyte retrieval was performed transvaginally and cumulus enclosed oocytes were matured for 28--30 h before evaluation. Prior to ICSI, all MII oocytes were graded into three groups according to the number of anomalies: grade I: oocytes without any anomaly (n = 144, 54%), grade II: oocytes with one anomaly (n = 87, 33%) and grade III: oocytes with at least two anomalies (n = 33, 12.5%). RESULTS: Oocyte grades did not differ between women with polycystic ovaries and women with normal ovaries. Morphology was not related to fertilization rates. The cleavage rate was, however, affected by morphological anomalies, although no significant decrease in cleavage rate could be demonstrated when all grade II and III oocytes were compared with normal oocytes. Significantly more embryos of good quality developed after grade I oocytes [54/144 (37.5%)] compared with those from grade II and grade III oocytes (22/120; P = 0.001). The presence of cytoplasmic abnormalities significantly decreased the cleavage rate (P = 0.04) and also the number of good quality embryos (P < 0.001). CONCLUSION: The in-vitro maturation of oocytes without anomalies yields higher quality embryos, with higher cleavage rates, than those with anomalies.

Fertil Steril 2002 Sep;78(3):515-9
Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization. Raziel A, Friedler S, Schachter M, Kasterstein E, Strassburger D, Ron-El R.
In Vitro Fertilization Unit, Assaf Harofeh Medical Center, Tel-Aviv University, Zerifin, Israel. araziel@asaf.health.gov.il
OBJECTIVE: To find the type and frequency of chromosomal abnormalities in a selected group of high-order implantation failure (> or =6 IVF trials and > or =15 transferred embryos) and to evaluate its impact on pregnancy outcome.DESIGN: A retrospective study.SETTING: In vitro fertilization (IVF) unit in a university affiliated hospital.PATIENT(S): Sixty-five couples with high-order implantation failure in IVF and embryo transfer.INTERVENTION(S): In vitro fertilization/embryo transfer (ET), work-up for implantation failure, cytogenetic analysis of the couple.MAIN OUTCOME MEASURE(S): We studied the type and frequency of chromosomal changes, quality of embryos, cumulative pregnancy rates, and pregnancy outcome.RESULT(S): The mean number of treatment cycles per patient, before karyotyping was 7.8 +/- 2.4 (range: 6 to 16 cycles). The mean cumulative number of all transferred embryos per patient was 25.7 +/- 10.3 (range: 9 to 65 embryos). Chromosomal abnormalities were found in 10 of 65 (15.4%) cases: translocations in six, mosaicism in two, and inversion or deletion in another two. The morphologic characteristics of the transferred embryos and the cumulative pregnancy rates were similar in patients with implantation failure with and without chromosomal changes. Three of the 16 patients with abnormal karyotype delivered and three miscarried within a follow-up period of 1 year.CONCLUSION(S): A high frequency of chromosomal aberrations was found in a selected group of high-order implantation failures, a similar frequency to recurrent miscarriages. Karyotyping is recommended as part of the work-up for repeated implantation failure in assisted reproduction. Treatment options include further IVF trials, preimplantation genetic diagnosis, or oocyte donation, tailored according to the type of chromosomal change. An international registry should be considered to assist in counseling these patients.

Int J Androl 2000;23 Suppl 2:20-5
Genetic screening for patients with azoospermia and severe oligo-asthenospermia. Chiang HS, Wei HJ, Chen YT.
Department of Urology; Department of Gynecology, Taipei Medical College, Taipei, Taiwan.
Carolina, USA. pmiller@ghs.org
In order to explore the genetic defects of patients with azoospermia or severe oligo-asthenospermia, screening examinations were carried out for the chromosome disorder and gene deletion of the Y chromosome for 220 male infertility patients. The present results show that the total prevalence of genetic defects is 23.6%, including 38 patients (28.4%) with chromosome disorder and 14 patients (16.8%) with gene deletion in the Yq arm. The most prevalent chromosome anomaly is 47XXY (Klinefelter's syndrome), which includes 18 cases of pure type and three cases of mosaic type. Variable autosomal translocations occurred in both the azoospermia group (5.2%) and the oligo-astheno-spermia group (5.8%) with similar prevalence. A total of 22 patients had deletions of the variable, interstitial portion of the Yq arm. These gene deletions are distributed not only inside the AZF region, but also outside of this region. The severity of deletions is not well correlated to the clinical testicular function of the patients. We conclude that chromosome disorder and gene deletions are the causative factors of patients with azoospermia and oligo-asthenospermia. Genetic screening should be a routine examination for them before the use of assisted-reproductive technologies.