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.

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.

Saving time during laparoscopy using a new, wall anchoring trocar device.

OBJECTIVE: Safe and reliable access systems are crucial in laparoscopy, and trocar dislodgement is still a common and frustrating problem. Wall emphysema can occur besides the risky prolongation of the surgical procedure. Wall-anchoring components provide a better hold of the device. This comparative analysis assesses the frequency of dislodgement and a time-sparing effect on the intervention of 3 different trocar systems, including an innovation in the field of access-providing systems. METHODS: Patients who underwent laparoscopy for various gynecological indications were included and randomized consecutively into 3 groups according to the access system used in the intervention: (A) trocar fitted with a spiral thread on the sleeve, (B) trocar with plain sleeve, (C) trocar as in B together with a fixator. This novelty is installed on the trocar before insertion and then sutured to the abdominal wall. Intervention time, frequency of trocar corrections, and the time loss through correction were registered. Standard statistical analyses were performed. RESULTS: The cohort comprised 131 patients; 51 patients were consecutively randomized into group A, 38 into group B, and 42 into group C. Mean intervention time was different, shortest in C and highest in B. Frequency of interruption of the intervention due to adjustment of the device and time loss through adjustment was lowest in group C (fixator + plain sleeve) and highest in group B (plain-sleeve) (0.47 vs 0.29, P<0.05 and 2.13 minutes vs 0.69 minutes, P<0.05). CONCLUSION: Wall-anchoring components lead to higher stability of ports and have a time-sparing effect. Comparing the 2 trocar groups with wall-anchoring properties (trocar with thread-fitted sleeve vs fixator + trocar with plain sleeve), the mean operation time was lowest in the fixator group, and the time-saving effect was higher.

Increased blastomere number in cleavage-stage embryos is associated with higher aneuploidy.

OBJECTIVE: To evaluate the relationship between blastomere number and aneuploidy. DESIGN: Historical cohort study. SETTING: In vitro fertilization clinic. PATIENT(S): Two hundred fifty-nine patients undergoing in vitro fertilization (IVF) in combination with comprehensive chromosomal screening of embryos. INTERVENTION(S): A total of 1,915 embryos were biopsied on day 3 and underwent comprehensive chromosomal screening with microarray-based comparative genomic hybridization. MAIN OUTCOME MEASURE(S): Relationship between day 3 blastomere number, aneuploidy rate, and progression to the blastocyst stage. RESULT(S): A number of day 3 blastomeres >9 was associated with significantly increased aneuploidy rates. Rapidly developing embryos were significantly more likely to blastulate regardless of their chromosomal status. Number of embryos per patient greater than 13 was independently associated with lower aneuploidy rates after controlling for maternal age. This trend was not significant with the use of a more clinically relevant threshold of greater than six embryos per patient. CONCLUSION(S): Embryos with 6-9 cells at the cleavage stage should be considered for transfer over embryos with >9 cells. Day 3 blastomere number may be used in conjunction with extended culture to improve selection of euploid embryos, especially when supernumerary embryos are available. Further studies are needed to show if these selection criteria improve clinical outcomes.

Evaluation of mixed protocols with Bravelle (human-derived FSH) and Repronex (hMG) to assess clinical efficacy (EMBRACE) in women undergoing in vitro fertilization.

OBJECTIVE: To compare the efficacy and safety of three different ratios of human-derived follicle-stimulating hormone/human menopausal gonadotropin (human-derived FSH:hMG, Bravelle and Repronex) mixed together in the same syringe and administered subcutaneously once daily, to in vitro fertilization (IVF) patients <34 years or 34 to 40 years of age. DESIGN: Two randomized, prospective, age stratified, IVF studies. SETTING: Twenty-one academic and private clinics with experience in IVF/embryo transfer (ET). PATIENT(S): Infertile premenopausal women undergoing IVF-ET. INTERVENTION(S): Pituitary suppression with leuprolide acetate, randomization to one of three treatment groups, followed by gonadotropin stimulation (GS) for up to 15 days. The human-derived FSH:hMG ratios were the following: Group 1, a 1:1 ratio throughout; Group 2, a 3:0 ratio that was changed to 1:1 after GS day 5; Group 3, a 2:1 ratio that was increased to 3:1, 4:1, or 5:1 after GS day 5, as needed. MAIN OUTCOME MEASURE(S): Mean number of oocytes retrieved; peak estradiol levels; dose and duration of stimulation; implantation rates; adverse events; injection site pain; and pregnancy and live birth rates. RESULT(S): Overall, women <34 years had higher E(2) levels, more oocytes retrieved, and improved implantation and live birth rates compared with women 34 to 40 years old. Nonetheless, each ratio of human-derived FSH:hMG produced comparable implantation rates, and continuing pregnancy and take-home baby rates. CONCLUSION(S): All three ratios of human-derived FSH:hMG in both age groups produced comparable pregnancy and live birth rates with similar safety results.

Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis.

OBJECTIVE: To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis. DESIGN: Prospective, randomized trial. SETTING: Three tertiary care assisted reproductive technology programs. PATIENT(S): IVF-ET candidates with surgically confirmed endometriosis. INTERVENTION(S): Twenty-five patients received three courses of a long-acting GnRH agonist, 3.75 mg i.m. every 28 days, followed by standard controlled ovarian hyperstimulation. Twenty-six patients received standard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens. MAIN OUTCOME MEASURE(S): Response to controlled ovarian hyperstimulation, ongoing pregnancy rates per cycle, group implantation rates, and implantation rate per embryo transfer procedure. RESULT(S): The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET. The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation, number of oocytes retrieved, fertilization rate, or number of embryos transferred. Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation rates (42.68% vs. 30.38%). CONCLUSION(S): Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis resulted in significantly higher ongoing pregnancy rates than did standard controlled ovarian hyperstimulation regimens. No deleterious effect on ovarian response was observed.

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.

Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization.

OBJECTIVE: To assess the relationship between maternal age, chromosome abnormality, implantation, and pregnancy loss. DESIGN: Multicenter retrospective study. SETTING: IVF centers in the United States. PATIENT(S): IVF patients undergoing chromosome screening. INTERVENTION(S): Embryo biopsy on day 3 or day 5/6 with preimplantation genetic diagnosis (PGD) by array comparative genomic hybridization. MAIN OUTCOME MEASURE(S): Aneuploidy, implantation, pregnancy, and loss rates. RESULT(S): Aneuploidy rates increased with maternal age from 53% to 93% for day 3 biopsies and from 32% to 85% for blastocyst biopsies. Implantation rates for euploid embryos for ages <35-42 years did not decrease after PGD: ranges 44%-32% for day 3 and 51%-40% for blastocyst. Ongoing pregnancy rates per transfer did not decrease for maternal ages <42 years after PGD with day 3 biopsy (48.5%-38.1%) or blastocyst biopsy (64.4%-54.5%). Patients >42 years old had implantation rates of 23.3% (day 3), 27.7% (day 5/6), and the pregnancy rate with day 3 biopsy was 9.3% and with day 5 biopsy 10.3%. CONCLUSION(S): Selective transfer of euploid embryos showed that implantation and pregnancy rates were not significantly different between reproductively younger and older patients up to age 42 years. Some patients who start an IVF cycle planning to have chromosome screening do not have euploid embryos available for transfer, a situation that increases with advancing maternal age. Mounting data suggests that the dramatic decline in IVF treatment success rates with female age is primarily caused by aneuploidy.

The effect of timing of embryonic progression on chromosomal abnormality.

OBJECTIVE: To evaluate the relationship between aneuploidy and timing of blastocyst formation. DESIGN: Historical cohort study. SETTING: Private IVF clinic. PATIENT(S): Ninety-four couples undergoing IVF treatment in combination with chromosomal screening of embryos. The mean maternal age was 39.2 years and average number of embryos per patient 5.3. INTERVENTION(S): A total of 530 embryos were biopsied on day 3 and underwent chromosome screening with microarray-based comparative genomic hybridization. MAIN OUTCOME MEASURE(S): Effect of day of embryo blastulation and morphologic grade on aneuploidy rate. RESULT(S): Day 5 morulas that progressed to blastocysts on day 6 were significantly less likely to be aneuploid (79.8%) than day 5 morulas that did not progress to blastocysts (92.9%). However, there was no significant difference in aneuploidy rates when embryos that became blastocysts on day 5 were directly compared with embryos that became blastocysts on day 6. CONCLUSION(S): Delayed blastulation is not associated with increased aneuploidy rates, but absence of blastulation is associated with increased aneuploidy. Therefore, we conclude that when choosing a morula for transfer on day 5, there may be a benefit in waiting an extra day for the possibility of blastulation to occur.

Successful outcome after preimplantation genetic screening and very delayed embryo transfer.

We report the positive outcome of a delayed single ET of a preimplantation genetic screening-defined embryo in an otherwise routine case of IVF-ET. To our knowledge, this is the first report of a fresh ET 48 hours longer than what is generally considered the limit of days after egg retrieval (six) to safely perform an ET.

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.

Rescue intracytoplasmic sperm injection and preimplantation genetic diagnosis in combination can result in pregnancy.

OBJECTIVE: To report the birth of a baby from the transfer of one embryo after rescue intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD). DESIGN: Case report. SETTING: IVF center. PATIENT(S): A 42-year-old G2P0020 woman with unexplained infertility. INTERVENTION(S): Rescue ICSI followed by PGD. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): Rescue ICSI was performed on seven unfertilized oocytes, which resulted in three embryos. The PGD analysis revealed one normal embryo, which was transferred and resulted in pregnancy and delivery. CONCLUSION(S): Rescue ICSI in combination with PGD can result in a successful pregnancy.

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.