Intracytoplasmic Sperm Injection-embryo Transfer Cycles Research Articles

Effect of gonadotropin releasing hormon agonist addition to routine luteal phase support in intracytoplasmic sperm injection-embryo transfer cycles on pregnancy rates and outcomes

Abstract: Aim: To investigate the effect of gonadotrophin releasing hormone agonist (GnRH-a) addition to luteal phase support (LPS) in intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles of GnRH-a long protocol and GnRH antagonist (GnRH-anta) protocol, on pregnancy rates and outcomes. Materials and Method: One hundred and eight infertile couples treated with ICSI-ET were included in this prospective randomized study. Patients were randomly divided into two groups to undergo two different ovarian stimulation protocols. GnRH-a iong protocol was applied to group I and GnRH-anta protocol was applied to group II. Women to be treated by each of the two protocols were also randomly assigned to one of the two subgroups. Subgroups Ib and IIb received leuprolide acetate (0.5 mg s.c.) injections on the 5th and 10th days after ET in addition to routine LPS [90 mg/day of vaginal progesterone plus 4 mg of 17β Estradiol]. Only routine LPS was given to other two subgroups (groups la and IIa). Results: The total number of retrieved oocytes and MII oocytes were significantly higher in group Ia than in group Ib. There were no differences between subgroups in groups I and II regarding clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, abortion, ongoing pregnancy and live birth rates. Conclusion: Addition of GnRH-a to routine LPS in ICSI-ET cycles of GnRH-a long protocol and GnRH-anta protocol seems to have no effect on ongoing pregnancy, abortion, multiple pregnancy, OHSS, clinical pregnancy and live birth rates.

The Effect of the Sperm Source on the Outcome of Intracytoplasmic Sperm Injection-Embryo Transfer Cycles in Normal Responder Women

Results: Patients were divided four group according to source of sperm and sperm parameters. Testicular spermatozoa obtained from men with azoospermia (group 1, n=43), severe oligoasthenoteratozoospermia (sOAT), (group 2, n=93), oligoasthenoteratozoospermia (OAT) (group 3, n=209) and normal semen analysis (group 4, n=539). The most reduced fertilization rate was observed with testicular spermatozoa and the fertilization rate increased as semen quality increased from Group 2 to 4. Our results indicated that semen quality can affect the fertilization process. We observed that the cleavage and high-quality embryo rates were highest in group I (88.4% and 93%, respectively) compared to other groups. Clinical outcomes of ICSI did not show statistically significant differences in the rates of clinical pregnancy, miscarriage and live birth rate. Conclusion: Neither sperm parameters nor the source of spermatozoa affects live birth rate in normoresponder women when motile/morphologically normal spermatozoa is present.

A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles

The aim of the present study was to compare the efficacy, tolerability and patients’ satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20–40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20 mg twice daily (n = 96) or micronized progesterone 400 mg twice daily at the day of oocyte retrieval (n = 114). The clinical success rate (31% versus 33%; p = 0.888), miscarriage rate (5.0% versus 3.0%; p = 0.721), ongoing pregnancy rate (30.0% versus 30.0%; p = 1.000), implantation (22.0% versus 24.0%; p = 0.254) and multiple pregnancy rate (5.30% versus 7.20%; p = 0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62 ± 13.83 ng/ml versus 20.66 ± 18.09 ng/ml; p = 0.001). However, there was no statistically significant difference regarding the patients’ satisfaction (p = 0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40 mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients’ satisfaction and tolerability, for LPS among women undergoing IVF.

A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle.

ObjectiveThe goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol.MethodsThis prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR.ResultsThe CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group (17.3±7.2 vs. 11.0±7.2; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes.ConclusionMeasuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.

Effect of chromosomal polymorphisms of different genders on fertilization rate of fresh IVF–ICSI embryo transfer cycles

To explore whether chromosomal polymorphisms of different genders affect outcomes of fresh IVF and intracytoplasmic sperm injection (ICSI) embryo transfer cycles differently, 37 couples with chromosomal polymorphisms were identified out of 614 infertile couples undergoing IVF–ICSI treatments. Group 1 included 20 couples in which only the male carried chromosomal polymorphisms; group 2 included 17 couples with female carriers only; group 3 included 19 infertile couples with normal karyotypes randomly selected as controls. A significantly lower fertilization rate was found in group 1 compared with groups 2 and 3 (56.68% in Group 1, 78.02% in group 2 and 71.74% in group 3; group 1 versus group 2, P < 0.001; group 1 versus group 3, P = 0.001; respectively). When stratified according to fertilization method, the fertilization rate in IVF cycles of group 1 was significantly lower than group 3 (50.00% in Group 1, 73.89% in Group 3, P < 0.001). Fertilization rates in ICSI cycles between groups 1 and 3 were not significantly different. This study suggests that male chromosomal polymorphisms adversely influence fertilization rates of IVF cycles. The use of ICSI may improve the success of infertility treatment by increasing the fertilization rate for men with chromosomal polymorphisms.

Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women

Antithyroid antibodies (ATA) are found in 5–15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA are associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. This study evaluated the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)–embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI–embryo transfer cycles were prospectively enrolled in this study. Women positive for at least one of the thyroid antibodies, with normal thyroid-stimulating hormone (TSH) and free T4 concentrations and negative for anticardiolipin antibodies and lupus anticoagulant were included. ICSI was performed for fertilization in all cycles. Of 253 women, 219 were ATA negative and 34 ATA positive. Implantation rates (19.1% versus 18.4%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. The presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women was not found to significantly affect the outcome of ICSI–embryo transfer cycles.Antithyroid antibodies (ATA) can interact with thyroid hormone receptors located on the human oocyte and impair the chance of fertilization and healthy pregnancy. They are found in 5–15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA have been reported to be associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. The objective of our study was to evaluate the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)–embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI–embryo transfer cycles were prospectively enrolled in this study. Women with at least one of the thyroid antibodies positive and normal TSH and free T4 concentrations were included in the study. Since other immunological disorders might affect the results, antiphospholipid antibodies (APA), which are the markers of antiphospholipid antibody syndrome, were also screened in all women prior to study. Women with positive for APA were excluded in the final analysis. Of 253 women, 219 (86.6%) were ATA negative and 34 (13.4%) ATA positive. Implantation rates (19.1% versus 18.4%), biochemical pregnancy rates (9.2% versus 14.3%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. In conclusion, presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women does not affect the outcome of ICSI–embryo transfer cycles.

Random anti-Müllerian hormone predicts ovarian response in women with high baseline follicle-stimulating hormone levels

To evaluate the predictive value of random serum anti-Müllerian hormone (AMH) in the assessment of ovarian response in patients with diminished ovarian reserve (DOR; diagnosed after the observation of elevated baseline levels of early follicular follicle-stimulating hormone [FSH]) who were undergoing intracytoplasmic sperm injection-embryo transfer (ICSI-ET) and to compare the random serum AMH and baseline FSH levels in these patients for the prediction of poor ovarian response. Retrospective study. University hospital. One hundred and thirty-nine patients who were undergoing ICSI-ET cycles with early follicular FSH level >9 IU/mL. None. Poor ovarian response in ICSI-ET cycles. For the identification of women at risk of cycle cancellation, an AMH cut-off level ≤1.2 ng/mL had 97.3 % sensitivity, 31.3 % specificity, 33.9 % positive predictive value, and 96.9 % negative predictive value in the women with high baseline FSH levels. An AMH cut-off level ≥1 ng/mL had a sensitivity of 58.7 % and specificity of 95.1 % for prediction of retrieval of 4 or more oocytes. By using a serum AMH cutoff level of 1.5 ng/mL, the ongoing pregnancies were predicted with 83.3 % sensitivity and 82.5 % specificity and yielded a positive predictive value of 31.2 % and a negative predictive value 98.1 %. Measurement of random serum AMH level is a useful tool in the prediction of ovarian response in patients with high serum early follicular FSH levels.

Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols

The efficacy of aromatase inhibitors incorporated in the ovarian stimulation protocols of poor-responder patients undergoing intracytoplasmic sperm injection-embryo transfer cycles was investigated. A total of 70 poor-responder patients were randomized into two groups on day 3 of their menstrual cycle. In Group A, an aromatase inhibitor (letrozole, 5 mg/day) was administered along with a fixed dosage (450 IU/day) of recombinant FSH (rFSH), whereas Group B were treated with the same rFSH dosage alone. A flexible regimen of gonadotrophin-releasing hormone antagonist was administered in both groups. The mean total dose of rFSH (2980 +/- 435 IU versus 3850 +/- 580 IU, P < 0.05) and serum concentrations of oestradiol on the day of human chorionic gonadotrophin administration (1870 +/- 159 pg/ml versus 2015 +/- 175 pg/ml, P < 0.05) were significantly lower in Group A compared with Group B, respectively. The rate of cycle cancellation due to poor ovarian response was lower in Group A (8.6%) than in Group B (28.6%), ( P < 0.05). The costs of achieving a clinical pregnancy were US$11560 and US$17584, and the clinical pregnancy rates per embryo transfer were 25.8% and 20%, in groups A and B, respectively. In conclusion, adjunctive letrozole administration seems to restore an IVF cycle by decreasing the rate of cycle cancellation and seems to reduce the cost by reducing the total gonadotrophin dosage.

The effect of pronuclear morphology on embryo quality parameters and blastocyst transfer outcome.

Embryo quality may be accurately assessed as early as the pronuclear zygote phase, as shown in recent studies. However, it is not known whether good quality zygotes are destined to become good quality cleavage stage embryos and blastocysts. In this retrospective study, 86 intracytoplasmic sperm injection-embryo transfer cycles were studied where each available embryo was scored from the zygote until the blastocyst stage. Embryonic normality parameters such as pronuclear pattern, early cleavage, cleavage stage embryo grade, the presence of embryos with > or =8 cells on day 3 and blastocyst quality were recorded. Embryo transfer was undertaken at the blastocyst stage and the outcome was studied according to the pronuclear pattern exhibited by the zygotes. Embryos that showed an ideal pronuclear pattern (0 PN pattern) cleaved earlier and faster and resulted in better quality cleavage stage embryos and blastocysts. The incidence of blastocyst formation was 72% in zygotes showing a 0 PN pattern, compared with 12.7% in zygotes with double pronuclear abnormality. Higher implantation and pregnancy rates were obtained when at least one blastocyst derived from a 0 PN pattern zygote was included in the set of embryos to be transferred. Our results indicate that the pronuclear pattern of the zygote is closely related to blastocyst formation and quality. Blastocysts derived from 0 PN zygotes have a higher potential for implantation.