Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials.

OBJECTIVE: To evaluate the usefulness of preimplantation genetic screening (PGS) using fluorescence in situ hybridization (FISH) for two different indications: repetitive implantation failure (RIF) and advanced maternal age (AMA). DESIGN: Two prospective, randomized controlled trials with patients allocated in two arms: blastocyst transfer on day 5 (group A) or PGS with transfer on day 5 (group B). SETTING: University-affiliated private clinics. PATIENT(S): The RIF study included women <40 years with three or more failed IVF cycles without other known causal factors (91 patients). The AMA study included intracytoplasmic sperm injection patients aged between 41 and 44 (183 patients). INTERVENTION(S): In the PGS group, single-cell day 3 biopsy was performed with aneuploidy screening for chromosomes 13, 15, 16, 17, 18, 21, 22, X, and Y. In both the blastocyst transfer group and the PGS group, ET was performed on day 5. MAIN OUTCOME MEASURE(S): Live-birth rate per patient and per started cycle. RESULT(S): A significant increase in live-birth rates per patient was found in the PGS group compared with the blastocyst group for the AMA study (30/93 patients [32.3%] vs. 14/90 patients [15.5%]; odds ratio, 2.585; confidence interval, [1.262-5.295]). In the RIF study no significant differences were observed (23/48 patients [47.9%] vs. 12/43 patients [27.9%]). CONCLUSION(S): PGS with FISH was shown to be beneficial for the AMA group.

Accumulation of oocytes: a new strategy for managing low-responder patients.

Accumulation of oocytes from several ovarian stimulation cycles is currently possible using novel vitrification technologies. This strategy could increase the inseminated cohort, creating a similar situation to normoresponders. This study included 242 low-responder (LR) patients (594 cycles) whose mature oocytes were accumulated by vitrification and inseminated simultaneously (LR-Accu-Vit) and 482 patients (588 cycles) undergoing IVF/embryo transfer with fresh oocytes in each stimulation cycle (LR-fresh). Drop-out rate in the LR-fresh group was >75%. The embryo-transfer cancellation per patient was significantly lower in the LR-Accu-Vit group (9.1%) than the LR-fresh group (34.0%). Live-birth rate (LBR)/patient was higher in the LR-Accu-Vit group (30.2%) than the LR-fresh group (22.4%). Cumulative LBR/patient was statistically higher in the LR-Accu-Vit group (36.4%) than the LR-fresh group (23.7%) and a similar outcome was observed among patients aged ⩾40years (LR-Accu-Vit 15.8% versus LR-fresh 7.1%). The LR-Accu-Vit group had more cycles with embryo cryopreservation (LR-Accu-Vit 28.9% versus LR-fresh 8.7%). Accumulation of oocytes by vitrification and simultaneous insemination represents a successful alternative for LR patients, yielding comparable success rates to those in normoresponders and avoiding adverse effects of a low response. The accumulation of oocytes from several ovarian stimulation cycles is currently possible with the aid of novel vitrification technologies. This strategy could be useful for low-responder patients, contributing to increase the inseminated cohort and creating a similar situation as in normal responders. According to the results presented herein (higher live-birth rate per patient treated), this strategy represents a successful alternative for low-responder patients, yielding comparable success rates to those in normal responders and avoiding the adverse effects of a low response.

Impact of luteinizing hormone administration on gonadotropin-releasing hormone antagonist cycles: an age-adjusted analysis.

OBJECTIVE: To analyze the impact of LH administration on cycle outcome in ovarian stimulation with GnRH antagonists. DESIGN: Randomized, open-label, controlled trial performed in two age subgroups. Recombinant (r) FSH versus rFSH + rLH administration was compared. SETTING: University-affiliated private infertility clinic. PATIENT(S): Up to 35 years old (n = 380) and aged 36 to 39 years (n = 340), undergoing their first or second IVF cycle. INTERVENTION(S): Recombinant LH administration since stimulation day 1. MAIN OUTCOME MEASURE(S): Implantation rate, ongoing pregnancy rate. RESULT(S): In the young population, implantation rates were similar: 27.8% versus 28.6%, odds ratio (OR) 1.03 (95% confidence interval [CI] 0.73-1.47), as was the ongoing pregnancy rate per started cycle: 37.4% versus 37.4%, OR 1.0 (95% CI 0.66-1.52). In older patients, the implantation rate was significantly higher in the rFSH + rLH group: 26.7% versus 18.6%, OR 1.56 (95% CI 1.04-2.33). Ongoing pregnancy rates per started cycle were 33.5% versus 25.3%, OR 1.49 (95% CI 0.93-2.38). CONCLUSION(S): Recombinant LH administration significantly increased the implantation rate in patients aged 36 to 39 years. A clinically relevant better ongoing pregnancy rate per started cycle was observed, although the difference was not statistically significant. Patients younger than 36 years do not obtain any benefit from rLH administration.

Twins born after transplantation of ovarian cortical tissue and oocyte vitrification.

OBJECTIVE: To present a combination of ovarian tissue and oocyte cryopreservation as an effective strategy for achieving pregnancy in a breast cancer patient. DESIGN: Case report. SETTING: Tertiary care university-affiliated hospital, tissue bank, and infertility clinic. PATIENT(S): A 36-year-old patient diagnosed with atypical medullar breast cancer and negative for estrogen, P, and HER2 receptors underwent ovarian tissue cryopreservation before receiving chemotherapy and radiotherapy. INTERVENTION(S): Laparoscopic ovarian cortex extraction, ovarian tissue cryopreservation, ovarian tissue thawing and transplantation, controlled ovarian stimulation (COS), oocyte retrieval, vitrification and IVF, and embryo culture and replacement. MAIN OUTCOME MEASURE(S): Resumption of spontaneous ovarian function after transplantation, response to COS, oocyte vitrification, IVF, pregnancy, and delivery. RESULT(S): Menses occurred 63 days after transplantation. Sixteen mature oocytes were obtained in four COS procedures. All vitrified oocytes survived warming, and 77.7% were fertilized. Two day 3 embryos were replaced, and two healthy boys were born at 34 weeks. CONCLUSION(S): Ovarian tissue cryopreservation and grafting preserves fertility. Simultaneous oocyte vitrification increases the success of assisted reproductive technology in poor-prognosis patients and avoids the consequences of the short lifespan of the transplanted tissue.

New options in assisted reproduction technology: the Cryotop method of oocyte vitrification.

The Cryotop vitrification method has been shown to be a very useful tool for oocyte cryopreservation, giving excellent results regarding survival and clinical outcome. There are several clinical situations in which oocyte cryopreservation provides solutions that have not been available to date. This report describes three of these situations: (i) a low-responder patient who needed a single gene diagnosis due to the presence of a genetic disease; (ii) a patient undergoing endometrial bleeding on the day of oocyte retrieval who was also affected by a genetic disorder; and (iii) a patient who failed to become pregnant after the donation of vitrified oocytes and subsequently had the re-vitrified surplus embryos transferred. The resolution of these cases provides evidence of the enormous potential of the Cryotop method as a tool within assisted reproduction technology.

Implantation is apparently unaffected by the dopamine agonist Cabergoline when administered to prevent ovarian hyperstimulation syndrome in women undergoing assisted reproduction treatment: a pilot study.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a result of ovarian overexpression of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR2). VEGF/VEGFR2 binding disrupts cellular junctions and increases vascular permeability (VP), a characteristic of OHSS, but enhances angiogenesis, which is a fundamental step in implantation. In animals, the dopamine agonist Cabergoline (Cb2) prevents VP without affecting angiogenesis. In humans, Cb2 averts OHSS, but a possible detrimental effect on angiogenesis and implantation has not been explored. A pilot study was designed to analyze whether or not Cb2 administration, as a procedure for preventing OHSS, affects the outcome of assisted reproduction treatment (ART). METHODS: A retrospective study with endpoints of implantation and ongoing/term pregnancy rates. Women (n = 35) at risk of OHSS (20-30 follicles developed and >20 oocytes collected) took a daily oral dose of 0.5 mg Cb2 for 8 days, beginning on the day of hCG. They were matched with controls treated during the same period and who were similar with respect to age, number and quality of the embryos replaced, embryonic stage at transfer and sperm quality. RESULTS: No difference was detected between the groups in fertilization, implantation or pregnancy rates. A total of 14 ongoing (beyond 32 weeks) or full term pregnancies were registered in each group. No major problem was detected during pregnancy or after delivery in any of these babies. CONCLUSIONS: Administration of Cb2 in order to prevent OHSS is safe and does not appear to affect ART outcome.

Serum luteinizing hormone in patients undergoing ovarian stimulation with gonadotropin-releasing hormone antagonists and recombinant follicle-stimulating hormone and its relationship with cycle outcome.

The serum LH was determined on days 3, 6, and 8 of stimulation and on the day of hCG in 110 normogonadotropic patients undergoing controlled ovarian hyperstimulation (COH) for IVF induced with GnRH antagonists and recombinant FSH, creating three groups of patients according to Tukey's hinges (percentiles 25 and 75) for each determination. No differences were observed between the number of oocytes recovered or the fertilization, implantation, and pregnancy rates (PR) of the groups, although patients with high serum LH levels during stimulation showed significantly higher serum E2 levels on the day of hCG.

Comparison of two different starting multiple dose gonadotropin-releasing hormone antagonist protocols in a selected group of in vitro fertilization-embryo transfer patients.

OBJECTIVE: To compare the efficacy of two starting protocols of multiple dose GnRH antagonists (GnRH-a). DESIGN: Prospective randomized controlled study. SETTING: In vitro fertilization-embryo transfer program at the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): One hundred nine patients undergoing controlled ovarian hyperstimulation (COH) with recombinant gonadotropins and GnRH-a (0.25 mg/d). INTERVENTION(S): Patients started GnRH-a administration on stimulation day 6 (group 1) or when the leading follicle reached a mean diameter of 14 mm (group 2). MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates; serum E(2) and LH levels during ovarian stimulation; days of stimulation and GnRH-a administration. RESULT(S): Days needed for ovarian stimulation were similar in both groups but there was a significant difference when comparing days of GnRH-a administration. Serum E(2) and LH followed similar curves in both groups. Implantation and pregnancy rates were 23.7% and 44.4 % in group 1 and 28.6% and 50.9 % in group 2 (P=not significant [NS]). CONCLUSION(S): The efficacy of the two starting protocols of the multiple dose GnRH-a evaluated in this study is similar; however, this remark can only be drawn for a selected group of patients.

Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome.

OBJECTIVE: To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. DESIGN: Prospective observational study. SETTING: In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. PATIENT(S): Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. INTERVENTION(S): Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. MAIN OUTCOME MEASURE(S): Cycles were grouped according to serum P level on the day of hCG administration (<1.2 ng/mL or > or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. RESULT(S): The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. CONCLUSION(S): Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.