Faculty Bibliography

OBJECTIVE: The use of OC is increasing. We know the human oocyte meiotic spindle (MS) is crucial to chromosome segregation and embryo development while the zona pellucida (ZP) aids in sperm binding and fertilization. Today, polarized microscopy (PM) affords non-invasive MS and ZP evaluation. All MII oocytes cryopreserved in our lab undergo PM MS and ZP assessment 2 h post-harvest. We compared OC cycle outcome in cases performed for MED vs. DR vs. OD. DESIGN: Retrospective. MATERIALS AND METHODS: All women were <40 y at time of OC. Tumors in the MED group included 13 GYN, 10 breast, 3 leukemia, 2 colon, 2 CNS & 1 sarcoma. All patients underwent standard ovarian stimulation followed by retrieval, PM for MS and ZP, then OC of MII oocytes. RESULTS: Cycle outcome is shown in the Table. (Table presented). CONCLUSIONS: The majority of retrieved oocytes in all groups were MII. Women diagnosed with malignancy achieved adequate ovarian stimulation, egg production and a similar number of spindle positive eggs compared to DR and OD patients, despite limited time for treatment and multiple outside stressors, including underlying disease. MS & ZP measurements were clinically comparable whether eggs were frozen for cancer, DR or OD

OBJECTIVE: The MS is critical to chromosome segregation and embryo competence. Today, polarized light microscopy (PM) affords non-invasive MS evaluation (MSE). We perform PM 2 h post-harvest and 1 h post-thaw. Here, we appraise its value. DESIGN: Retrospective. MATERIALS AND METHODS: 28 OC cycles with thaw were assessed; 1/2 eggs were slow frozen and 1/2 vitrified (vit); pt's eggs were split between methods. MSE was done in the last 23 cycles. Outcome measures included 2PN fertilization (2PN-F), embryo quality suitable for ET, blast formation rate (BFR), and embryo usability (transferred or refrozen). RESULTS: All eggs were from women <38 (mean 31) yowith normal D3 FSH/E2. Of 28 cycles, 57% had pregnancy; 12 delivered 17 liveborns, 3 are ongoing and 1 aborted. In the last 25 cycles, 286 MII eggs were thawed after cryo for a mean of 3 mos; pre-cryo, 83% were MS positive (SP+). 255 (89%) survived; 89% were SP+ post-thaw, a 94% pre-cryo and post-thaw MSE correlation. 211 (83%) ICSI'd eggs achieved 2PN-F. 2.3 embryos were transferred/cycle (30 slow & 22 vit). Pre-cryo MSE: no difference was noted in egg survival or 2PN-F. 65% of SP+ vs. 44% of MS negative (SP-) zygotes became embryos suitable for ET D3 post-thaw (p=.02). No difference was noted in the BFR or % of embryos suitable for D5 ET, but 86% of embryos transferred or refrozen were from SP+ eggs. Post-thaw MSE: no difference was noted in the % of embryos suitable for ET D3 post-thaw or BFR. A significantly higher % of embryos were suitable for ET D5 post-thaw in the SP+ (57%) vs. SP- (29%) groups (p=.03) and 95% of transferred or refrozen embryos were from SP+ oocytes. When comparing MSE data for slow vs. vit eggs, no differences were noted. CONCLUSIONS: Most retrieved oocytes (slow and vit) exhibited a MS pre & post-thaw and most transferred or refrozen embryos were from SP+ oocytes. OC does not appear to damage the MS and viewing it may correlate with oocyte competence. Because MSE may improve efficiency of gamete selection, it should be considered to advance the field of OC

OBJECTIVE: As more reproductive-age women are diagnosed with and survive cancer, OC use is increasing as a means of FP, particularly in those without a male partner. We compared outcomes of medically-indicated (MED) OC cycles to those of infertile women completing an OC thaw cycle (THAW), including their meiotic spindle evaluation (MSE). All MII oocytes cryopreserved in our lab undergo MSE 2 h post-harvest. DESIGN: Retrospective. MATERIALS AND METHODS: 31 MED (520 retrieved eggs) and 28 THAW (512 retrieved eggs) OC cycles were reviewed. Tumors in the MED group included 13 GYN, 10 breast, 3 leukemia, 2 colon, 2 CNS and 1 sarcoma. All patients underwent standard ovarian hyperstimulation followed by retrieval, MSE 2 h post-harvest, then OC of all MII oocytes. Both slow freezing and vitrification were used. 4 MED pts froze ¹?₂ as zygotes. RESULTS: In the THAW cycles, there were 16 (57%) pregnancies: 12 women delivered 17 liveborns (5 twins), 3 have ongoing gestations and 1 miscarried. 90% of eggs survived and there was a 94% pre-cryo to post-THAW MSE correlation. 2 MED thaw cycles resulted in 1 pregnancy. Cycle comparisons for THAW vs. MED are shown in the Table. (Table presented). CONCLUSIONS: The majority of oocytes in both groups were mature (MII) and exhibited a spindle. Women diagnosed with cancer can achieve adequate ovarian stimulation, egg production and MSE despite limited time to complete OC treatment and multiple outside stressors, including their underlying disease and its management. Based on our preliminary THAW data, we believe cancer pts should have a reasonable chance for pregnancy using their frozen eggs

This study assessed 1908 embryos, including those with abnormal numbers of pronuclei, in IVF cycles from July 2001 to December 2006 in which preimplantation genetic screening (PGS) was performed on day 3 post-retrieval and 'euploid' embryos transferred the following day. PGS-intracytoplasmic sperm injection and PGS-translocation cycles were excluded. At 18 h post-insemination, the zygote distribution was 19% 0PN, 4% 1PN, 69% 2PN and 8% 3PN. No pregnancy occurred following 0PN or 1PN embryo transfers. A retrospective, blinded morphological ranking of all embryos on day 3 was performed and the results compared with PGS; no 0PN or 1PN embryo would have been chosen for transfer based on morphological superiority alone. Blastocyst formation occurred in 1PN embryos (29%) but not in 0PN embryos when evaluated on day 5. Euploid karyotypes were reported for biopsies of 0PN (3%), 1PN (5%) and 2PN (19%) embryos (P = 0.015, 1PN versus 2PN). A Y chromosome was observed in 0PN (17%) and 1PN (32%) embryos; surprisingly, 91% of these Y chromosome-bearing embryos were aneuploid. Many different meiotic and fertilization errors can result in 0PN or 1PN zygotes; these results indicate that the resultant embryos should not be transferred, especially when normally fertilized embryos are available

OBJECTIVE: To reevaluate clinical management of isolated teratozoospermia, in couples initiating IVF. DESIGN: Retrospective analysis of fertility indices in 535 cycles. SETTING: A large, university-based fertility center. PATIENT(S): Consecutive couples (n = 495) who had a semen analysis using Kruger/Tyberberg strict criteria at our center within 12 months before undergoing their first and/or second IVF cycle in 2002-2004 with >2 million postwash, motile sperm on the day of egg retrieval. INTERVENTION(S): Eggs were fertilized either by conventional IVF or ICSI. Semen analysis and gamete/embryo manipulation was standardized in all cases. MAIN OUTCOME MEASURE(S): Fertilization, fertilization failure, pregnancy, and live birth rates. RESULT(S): There was no statistical difference in fertilization, fertilization failure, pregnancy, and live birth rates in the first or second IVF cycle when comparing couples with isolated teratozoospermia (<5% normal morphology) to those with a normal semen analysis. Furthermore, no improvement in these outcomes was noted when ICSI was used to treat these teratozoospermic couples. CONCLUSION(S): Because isolated teratozoospermia generally does not impact on the major indices of IVF, these patients need not be subjected to the unnecessary cost and potential risks of ICSI. Future studies, however, should focus on different sperm morphologic and biochemical parameters to determine if they are important for clinical management in IVF

OBJECTIVE: To report a case of a heterotopic primary abdominal pregnancy after two-blastocyst IVF-ET. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A woman with a heterotopic abdominal pregnancy after IVF-ET. INTERVENTION(S): Pituitary down-regulation with luteal antagon, ovulation induction with menotropins, IVF-ET, progesterone in oil for luteal support, dilation and curettage for missed abortion, laparoscopy, and resection of abdominal gestation. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin levels, pelvic ultrasound examinations, and laparoscopic and pathologic findings. RESULT(S): A heterotopic abdominal pregnancy occurred after a two-blastocyst IVF-ET. The concurrent intrauterine gestation resulted in a miscarriage. CONCLUSION(S): The number of embryos transferred has been identified as a powerful risk factor for heterotopic pregnancy; however, heterotopic pregnancy can occur following a two-embryo, blastocyst stage transfer

We describe our experience of over 300 cycles of preimplantation genetic diagnosis (PGD) and report clinical pregnancy rates (35%-67%) that support using this technology to screen for genetic disorders and chromosomal abnormalities. In clinical practice for over ten years, PGD offers couples the earliest form of genetic screening and may help improve ongoing pregnancy rates in poor-prognosis patients

A randomized clinical trial of 406 patients with advanced maternal age by Mastenbroek and co-workers recently published in the New England Journal of Medicine showed a significant decrease in pregnancy outcome after preimplantation genetic screening (PGS). It is our opinion that this study suffers from a number of insurmountable inaccuracies and that these are either a direct consequence of the inexperience of the team or of a general disregard of vital guidelines reported in the literature. Most importantly, the authors show that in their hands embryo biopsy may affect as many as half the embryos. The error rate was not presented, shedding doubt on the authors' abilities to reliably diagnose the biopsied cells. An evaluation of the study indicates that poor biopsy technique, sub standard fixation and FISH methods, poor IVF outcomes and inappropriate patient selection are the cause of the discouraging results obtained by these authors rather than problems inherent to PGS

The intent of this study was to evaluate a recent randomized clinical trial evaluating the effect of preimplantation genetic screening (PGS) that reports a negative effect on pregnancy outcome. This article reviews appropriate PGS techniques and how they differ from the trial in question. A closer look at the clinical trial in question reveals significant lack of expertise in biopsy, cell fixation, genetic analysis, and patient selection. At most, this trial demonstrates that in inexperienced hands, PGS can be detrimental. No other conclusions concerning the effect of PGS on pregnancy results can be drawn from the trial.