Clinical utility of the endometrial receptivity analysis in women with prior failed transfers.

PURPOSE: To determine the utility of the endometrial receptivity analysis (ERA) in women with prior failed embryo transfers (ET). METHODS: This was a retrospective study of patients who underwent an ERA test with a subsequent frozen ET. Women were classified based on their indication for an ERA test: (1) ≥ 1 prior failed ET (cases), or (2) as a prophylactic measure (controls). A subset analysis of women with ≥ 3 prior failed transfers was performed. Pregnancy outcomes of the subsequent cycle were examined, including conception, clinical pregnancy, and ongoing pregnancy/live birth. RESULTS: A total of 222 women were included, 131 (59%) women with ≥ 1 prior failed ET and 91 (41%) controls. Among the 131 women with ≥ 1 prior failed ET, 20 women (9%) had ≥ 3 prior failed ETs. The proportion of non-receptive ERA tests in the three groups were the following: 45% (≥ 1 prior failed ET), 40% (≥ 3 prior failed ETs), and 52% (controls). The results did not differ between cases and controls. The pregnancy outcomes did not differ between women with ≥ 1 prior failed ET and controls. In women with ≥ 3 prior failed ETs, there was a lower ongoing pregnancy/live birth rate (28% vs 54%, P = 0.046). CONCLUSION: Women with ≥ 1 prior failed ET and ≥ 3 prior failed ETs had a similar prevalence of non-receptive endometrium compared to controls. Women with ≥ 3 prior failed ETs had a lower ongoing pregnancy/live birth rate despite a personalized FET, suggesting that there are additional factors in implantation failure beyond an adjustment in progesterone exposure.

Endometrial compaction does not predict live birth rate in single euploid frozen embryo transfer cycles.

PURPOSE: To evaluate whether endometrial compaction using sequential transvaginal ultrasound is associated with improved live birth rates in medicated single euploid frozen embryo transfer (FET) cycles. METHODS: Prospective observational cohort study at a private fertility clinic. Patients who underwent FETs between January and December 2018 were assessed for inclusion. The change in endometrial thickness between the end of the estrogen phase and the day before embryo transfer, measured by sequential transvaginal ultrasound, was used to categorize cycles with compaction (≥ 5%), no change, or expansion (≥ 5%). FET cycle outcomes were then compared between groups. The primary outcome was live birth. Secondary outcomes include clinical pregnancy rate and rate of spontaneous abortion. RESULTS: Of the 259 single euploid medicated FETs performed during the study period, only 43/259 (16.6%) of the cycles demonstrated ≥ 5% compaction, whereas 152/259 (58.7%) expanded and 64/259 (24.7%) were unchanged. Live birth rates did not differ between cycles with compaction (58.1%), no change (54.7%), or expansion (58.6%), p = 0.96. Clinical pregnancy and spontaneous abortion rates were also similar between groups. CONCLUSION: The vast majority of cycles did not demonstrate endometrial compaction. Endometrial compaction is not associated with live birth rate or spontaneous abortion rate in medicated single euploid FETs in this cohort.

Chromosome abnormalities in embryos derived from microsurgical epididymal sperm aspiration and testicular sperm extraction.

OBJECTIVE: To evaluate the patterns of chromosome abnormalities in embryos derived from intracytoplasmic sperm injection (ICSI) in microsurgical epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE) in comparison to embryos that are derived from naturally ejaculated (EJAC) patients. MATERIALS AND METHODS: Male partners with azoospermia who required MESA or TESE for ICSI were studied for chromosomal abnormalities. The ICSI patients with EJAC sperm served as the control group. Preimplantation genetic diagnosis (PGD) was performed by fluorescence in situ hybridization (FISH). Chromosome abnormalities were categorized as polyploidy, haploidy, aneuploidy, and complex abnormality (which involves more than two chromosomes). Fertilization, embryo development, and patterns of chromosome abnormalities were accessed and evaluated. RESULTS: There was no difference between the MESA, TESE, and EJAC patient groups in the rates of fertilization and pregnancy and the percentages of euploid embryos. In all three groups, less than one-half of the embryos for each group were normal (41 ± 31%, 48 ± 38%, and 48 ± 31% in MESA, TESA, and EJAC, respectively). Complex chromosomal abnormality was significantly more frequent in the MESA group than in the EJAC group (48.3% vs. 26.5%, respectively; p < 0.001). Furthermore, the overall pattern of chromosomal aneuploidy was similar among all three studied groups. CONCLUSION: We suggest that MESA and TESE, followed by ICSI and PGD, appear to be acceptable approaches for treating men with severe spermatogenesis impairment.

Ovarian reserve following uterine artery embolization in women of reproductive age: a preliminary report.

OBJECTIVE: To evaluate the effect of uterine artery embolization (UAE) for leiomyomata on reproductive potential for women in their reproductive age group. MATERIAL AND METHODS: This non-randomized, cross-sectional, observational study of ovarian reserve in women under 40 years of age who underwent UAE was conducted at a private practice located in Los Angeles, California. Twenty four women under 40 years of age who underwent UAE at least four months prior to study interventions were recruited. The study involved a one-time serum blood test on day three of the menstrual cycle and measured early follicular phrase follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) levels. RESULTS: Descriptive analysis showed means of all outcome measures were within normal range of values [FSH = 6.67IU/L (SD = 2.3), AMH = 1.24 ng/ml (SD = 0.9), E2 = 58.8 pg/ml (SD = 18.0)]. CONCLUSION: Hormonal findings from this study were within normal ranges, suggesting that ovarian function is not adversely affected by UAE. Women with fibroids within reproductive age may consider UAE as a treatment option.

Array CGH analysis shows that aneuploidy is not related to the number of embryos generated.

This study retrospectively analysed array comparative genomic hybridization (CGH) results of 7753 embryos from 990 patients to determine the frequency of embryonic euploidy and its relationship with the cohort size (i.e. the number of embryos available for biopsy and array CGH analysis). Linear regression analysis was performed to assess the effect of cohort size on euploidy rate adjusted for the effect of female age. While increasing female age was associated with a significant decrease in euploidy rate of day-3 and day-5 embryos (P<0.001 for both groups), cohort size was not significantly associated with euploidy rate. Logistic regression analysis was performed to assess the effect of cohort size, adjusted for maternal age, on the likelihood of having at least one euploid embryo available for transfer. The odds of having at least one euploid embryo in an assisted cycle was significantly decreased by increasing female age (P<0.01 for both day-3 and day-5 embryos) and was significantly increased by every additional embryo available for analysis (P<0.001 for both day-3 and day-5 embryos).

Accuracy of FISH analysis in predicting chromosomal status in patients undergoing preimplantation genetic diagnosis.

OBJECTIVE: The purpose of this study was to determine the positive predictive value (PPV) and negative predictive value (NPV) of FISH analysis and to determine which chromosomal abnormalities are most frequently confirmed. DESIGN: Prospective observational. SETTING: IVF laboratory. PATIENT(S): Two hundred forty-one embryos were analyzed from 98 patients. INTERVENTION(S): FISH reanalysis. MAIN OUTCOME MEASURE(S): Embryos that would have been discarded in patients undergoing preimplantation genetic diagnosis (PGD) were fixed and FISH reanalysis was performed. Results of reanalysis were compared with the day 3 diagnosis while PPV and NPV were calculated. RESULT(S): Among the 241 embryos, 198 embryos were abnormal and 43 were normal by day 3 FISH analysis. The PPV was 83% and the NPV was 81%. PPV was also determined for specific categories of aneuploidy, and certain abnormalities such as monosomies, trisomies, tetrasomies, and polyploidies were frequently confirmed on reanalysis (PPV >80%), whereas Turner syndrome diagnosis was not (PPV = 17%). CONCLUSION(S): FISH analysis offers a PPV of 83% and NPV of 81% when evaluating a single blastomere in conjunction with PGD. FISH errors and mosaicism are primarily responsible for the errors associated with FISH analysis in PGD.

Fluorescence in situ hybridization reanalysis of day-6 human blastocysts diagnosed with aneuploidy on day 3.

OBJECTIVE: To determine the concordance of day-6 blastocyst analysis with the day-3 fluorescence in situ hybridization (FISH) aneuploidy diagnosis. DESIGN: Retrospective study. SETTING: In vitro fertilization laboratory. PATIENT(S): Six hundred sixty embryos were included from 94 IVF/intracytoplasmic sperm injection patients undergoing preimplantation genetic diagnosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Single blastomeres biopsied on day 3. Aneuploidy screening for chromosomes 13, 18, 21, X, and Y were analyzed. Left-over blastocysts were reanalyzed on day 6. RESULT(S): Among the 660 embryos evaluated, 367 (55.6%) were euploid and 281 (42.6%) were aneuploid. Of the euploid embryos, 213 embryos were transferred, 68 were frozen on day 5, and 86 were left. All 281 aneuploid embryos were further cultured, and 55 (19.6%) progressed to blastocysts. When FISH reanalysis was performed, 33 of 55 blastocysts (60%) were confirmed aneuploid in concordance with the day-3 diagnosis. However, 22 of 55 blastocysts (40%) were determined to be euploid. In addition, 207 aneuploid embryos (73.7%) arrested before day 6, as opposed to 32 of the 86 euploid embryos (37.2%). CONCLUSION(S): Day-3 single-cell embryo biopsy reveals that aneuploidy can be confirmed in 60.7% of the blastocysts on reanalysis. The majority of discordance is most likely due to embryo mosaicism and possibly a limited ability to "self-correct."

Three dimensional/four dimensional ultrasound-guided embryo transfer using the maximal implantation potential point.

OBJECTIVE: To evaluate the use of maximal implantation potential (MIP) point in conjunction with a 3D/4D ultrasound in order to facilitate embryo transfers and potentially improve pregnancy rate. DESIGN: Retrospective, observational study. SETTING: IVF Center. PATIENT(S): Between October 1, 2002, and August 27, 2004, 1,222 patients who underwent 3D/4D-ultrasound guided embryo transfers. INTERVENTION(S): Ultrasound-guided embryo transfer using a 3D/4D ultrasound machine and the MIP point. MAIN OUTCOME MEASURE(S): Procedure feasibility with improved visibility. RESULT(S): Embryo transfers were performed at the MIP point and the pregnancy rate was 36.66% (average patient age, 37.6 years). Physicians reported improved visualization and a greater accuracy in the placement of embryos within the uterine cavity. CONCLUSION(S): The MIP point can be immediately identified and individualized for each patient. Embryo transfers at the MIP were associated with good implantation and pregnancy rates.

Is gender selection an appropriate use of medical resources?

Gender selection by PGD is an appropriate use of medical resources. Children borne through PGD for gender determination would be welcome and would come into a couple's life at a planned, opportune time. If the practice were made more available through insurance coverage, the size and makeup of families could become a matter of choice rather than chance for couples favoring this approach.