Cengiz Alatas

Blastocyst quality affects the success of blastocyst-stage embryo transfer

OBJECTIVE To determine the relationship between blastocyst quality and the results of embryo transfer at the blastocyst stage. DESIGN Retrospective case analysis. SETTING Tertiary care private hospital IVF center. PATIENT(S) A total of 350 blastocyst-stage embryo transfer cycles. INTERVENTION(S) In vitro culture to the blastocyst stage was undertaken in 350 ICSI cycles where four or more cleavage-stage embryos were available on day 3. MAIN OUTCOME MEASURE(S) Relationship between blastocyst quality and implantation and clinical and multiple pregnancy rates. RESULT(S) Transfer of at least one grade 1 or grade 2 blastocyst or one hatching blastocyst was associated with very high implantation and pregnancy rates. However, transfer of grade 3 blastocysts yielded very low implantation and pregnancy rates. CONCLUSION(S) There appears to be a strong correlation between blastocyst quality and success of blastocyst transfer.

Clinical outcome of intracytoplasmic injection of spermatozoa morphologically selected under high magnification: a prospective randomized study

Recent evidence shows that the selection of spermatozoa based on the analysis of morphology under high magnification (×6000) may have a positive impact on embryo development in cases with severe male factor infertility and/or previous implantation failures. The objective of this prospective randomized study was to compare the clinical outcome of 87 intracytoplasmic morphologically selected sperm injection (IMSI) cycles with 81 conventional intracytoplasmic sperm injection (ICSI) cycles in an unselected infertile population. IMSI did not provide a significant improvement in the clinical outcome compared with ICSI although there were trends for higher implantation (28.9% versus 19.5%), clinical pregnancy (54.0% versus 44.4%) and live birth rates (43.7% versus 38.3%) in the IMSI group. However, severe male factor patients benefited from the IMSI procedure as shown by significantly higher implantation rates compared with their counterparts in the ICSI group (29.6% versus 15.2%, P=0.01). These results suggest that IMSI may improve IVF success rates in a selected group of patients with male factor infertility. New technological developments enable the real time examination of motile spermatozoa with an inverted light microscope equipped with high-power differential interference contrast optics, enhanced by digital imaging. High magnification (over ×6000) provides the identification of spermatozoa with a normal nucleus and nuclear content. Intracytoplasmic injection of spermatozoa selected according to fine nuclear morphology under high magnification may improve the clinical outcome in cases with severe male factor infertility.

High implantation and pregnancy rates with testicular sperm extraction and intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia

Thirty-two infertile couples with obstructive and non-obstructive azoospermia were included in this study. Testicular sperm extraction (TESE) was performed in 16 obstructive azoospermic cases where microsurgical sperm aspiration (MESA) or percutaneous sperm aspiration (PESA) were impossible because of totally destroyed epididymis and 16 non-obstructive azoospermia cases with severe spermatogenetic defect where the testicles were the only source of sperm cells. A total of 288 oocytes was obtained from 32 females and 84% were injected. The fertilization rates (FR) with 2 pronuclei (PN) and cleavage rate were 50.8 and 68.2% respectively. A total of 15 pregnancies was achieved (53% per embryo transfer), nine from the obstructive and six from the non-obstructive group. Four pregnancies resulted in clinical abortion (26.6%). The ongoing pregnancy rate was 39.2% per embryo transfer (ET) and 34.3% per started cycle. A high implantation rate was also achieved (26.6% in non-obstructive and 30% in obstructive azoospermia group). Using testicular spermatozoa in combination with ICSI in both obstructive and non-obstructive azoospermic groups, high implantation and pregnancy rates can be achieved.

Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial

BACKGROUND The pathology underlying recurrent implantation failures (RIF) is not clear and treatment options proposed are generally not evidence based. Although the effect of heparin on trophoblast biology has not been studied extensively, given the available data suggesting a possible beneficial effect of heparin on embryo implantation, we decided to undertake this pilot study. METHODS One hundred and fifty women with > or =2 failed assisted reproduction treatment cycles were included in this randomized open-label pilot trial. Participants underwent controlled ovarian stimulation with the long protocol and were randomly allocated to receive 1 mg/kg/day low molecular weight heparin (LMWH) or no treatment in addition to routine luteal phase support (LPS) on the day after oocyte retrieval. LPS and LMWH was continued up to the 12th gestational week in pregnant participants. RESULTS There were 26 (34.7%) live births in the LMWH group, and 20 (26.7%) in the control group (absolute difference 8.0%, 95% CI -4.2 to 24.9%, P = 0.29). There were 34 (45.3%) and 29 (38.7%) clinical pregnancies in the LMWH and control groups, respectively (absolute difference 6.6%, 95% CI -9.0 to 21.8%, P = 0.41). Implantation rates were 24.5 and 19.8% in the LMWH and control groups, respectively (absolute difference 4.7%, 95% CI -4.7 to 14.1%, P = 0.33). CONCLUSION Despite lack of statistical significance, observed relative increase by 30% in live birth rates with LMWH may be regarded as a clinically significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment. Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study.

Blastocyst-stage transfer of poor-quality cleavage-stage embryos results in higher implantation rates.

OBJECTIVE To determine the feasibility and success of blastocyst-stage embryo transfers in patients having only fair and poor quality cleavage-stage embryos on day 3. DESIGN Prospective case study with historic controls. SETTING Tertiary care private hospital IVF center. PATIENT(S) A total of 158 day 5 embryo transfer cycles in patients with grade 3 and grade 4 cleavage-stage embryos. Control group consisted of 162 day 3 transfer cycles performed with embryos of similar quality. INTERVENTION(S) In vitro culture of embryos up to the blastocyst stage. MAIN OUTCOME MEASURE(S) The percentage of cycles that culminated in the transfer of at least one blastocyst and implantation and pregnancy rate related to the day of transfer. RESULT(S) In the day 3 transfer group, a mean of 5.2 embryos were replaced per patient. This was significantly more than the mean of 2.4 embryos that could be replaced on day 5 (P <.001). The clinical pregnancy rate per embryo transfer was 27.2% and 33.5% in the two groups, respectively (P >.05). The implantation rate per embryo was significantly higher in the day 5 transfer group (15% vs. 5.9%). The multiple pregnancy and abortion rates were similar between the groups. CONCLUSION(S) Transfer of fair and poor quality embryos at the blastocyst stage is feasible and is associated with higher implantation rates as compared to transfer of similar quality embryos on day 3.

Low-dose aspirin does not increase implantation rates in patients undergoing intracytoplasmic sperm injection : A prospective randomized study

AbstractPurpose: The aim was to evaluate the effect of aspirin on pregnancy and implantation rates in an unselected group of patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Two hundred and seventy-nine patients were randomized to receive 80 mg of aspirin (n = 139) or no treatment (r = 136) starting from the first day of controlled ovarian hyperstimulation. Results: Duration of stimulation, gonadotropin consumption, peak estradiol, number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar in the two groups. Implantation and clinical pregnancy rates were 15.6% and 39.6% versus 15.1% and 43.4% in aspirin treated and untreated groups, respectively (P > 0.05). Conclusions: Low-dose aspirin administration does not improve implantation and pregnancy rates in an unselected group of patients undergoing ICSI.

Elevated serum progesterone level on the day of human chorionic gonadotropin administration does not adversely affect implantation rates after intracytoplasmic sperm injection and embryo transfer

OBJECTIVE To evaluate the association between serum P levels on the day of hCG administration and the outcome of intracytoplasmic sperm injection (ICSI). DESIGN Retrospective case study. SETTING Assisted reproduction unit of a tertiary care private hospital. PATIENT(S) Nine hundred eleven ICSI cycles that proceeded to ET were studied. INTERVENTION(S) The decision to administer hCG was based on serum E2 levels and follicle size. Serum P was measured from frozen sera obtained on the day of hCG administration. Cycles were stratified according to serum P levels of <0.9 ng/mL (n = 298) or > or =0.9 ng/mL (n = 613). This cutoff level was selected because it yielded the highest sensitivity and specificity according to a receiver operator characteristic curve. MAIN OUTCOME MEASURE(S) Implantation and clinical pregnancy rates. RESULT(S) In cycles with high serum P levels, more oocytes were retrieved and more embryos were available for transfer. Clinical pregnancy rates per ET in the low and high P groups were 36.9% and 45.4%, respectively (P<.05). The implantation rate per embryo was similar in the two groups (14.9% and 16.4%, respectively, in cycles with P levels <0.9 vs > or =0.9 ng/mL). Abortion rates were 22.7 and 25.8%, respectively (P>.05). CONCLUSION(S) Our data showed no adverse effect of high serum P levels on the day of hCG administration on implantation rates after ICSI and ET.

Removal of unilateral endometriomas is associated with immediate and sustained reduction in ovarian reserve.

Endometrioma surgery by stripping the cyst capsule has been associated with a reduction in ovarian reserve. It is still not clear whether the inflicted damage is immediate, sustained over time or associated with the use of electrocautery, nor which marker is more accurately reflects the post-operative reduction in ovarian reserve. This observational study assessed the damage inflicted by endometrioma removal with anti-Müllerian hormone (AMH) concentration and antral follicle count (AFC) pre and post-operatively. Twenty-five women with unilateral endometrioma underwent laparoscopic stripping of the endometrioma cyst capsule. There was a significant decrease both in AMH concentration (24%) and in AFC (11%) 1 month following surgery (P<0.01). At 6months post-operatively, the respective values were 24% and 15% less than preoperatively. AMH concentration and AFC showed no correlation with the use of bipolar electrocautery during surgery. Primordial follicles embedded adjacent to the cyst capsule were found in 61.5% of the specimens. Endometrioma surgery by stripping of the cyst capsule is associated with a significant reduction in ovarian reserve. The reduction is immediate and sustained over time. AMH appears to be a better indicator for post-operative quantification of the ovarian reserve.

Impact of oocyte pre-incubation time on fertilization, embryo quality and pregnancy rate after intracytoplasmic sperm injection

Although, it is well known that pre-incubation of oocytes prior to conventional IVF improves fertilization and pregnancy rates, there are conflicting results regarding the effect of pre-incubation time in ICSI. This study evaluated the role of pre-incubation of oocytes on outcome in intracytoplasmic sperm injection (ICSI) cycles. A total of 1260 patients undergoing their first ICSI cycles were evaluated retrospectively. In patients undergoing ICSI during the year 2000 (Group I, n = 670), oocytes were injected immediately after retrieval, whereas in patients undergoing ICSI during 2001 (Group II, n = 590), oocytes were incubated for 2-4 h prior to injection. The mean age of patients was 33.9 +/- 5.04 years and 34.1 +/- 5.06 years in groups I and II, respectively. The number of oocytes with a first polar body (MII) and fertilization and cleavage rates were higher, and embryo quality was significantly better in group II. In contrast, the total numbers of oocytes without a first polar body (MI), those where germinal vesicle breakdown had not occurred (GV), and empty zona oocytes were higher in group I. No difference was found in the number of embryos transferred or implantation or clinical pregnancy rates. This study demonstrated that pre-incubation of oocytes prior to ICSI is associated with improved maturation of oocytes, fertilization and embryo quality.

The effect of uterine volume on uterine artery Doppler velocimetry in the myomatous state

This study aimed at testing the hypothesis that lower uterine arterial (UA) Doppler indices are caused by increased uterine volume rather than the presence of myoma. Uterine volumes were calculated and uterine and/or myomal arterial pulsatility index (PI) and resistance index (RI) were obtained by transvaginal color Doppler ultrasonography. The mean uterine volume in the myomatous group (276.2 cm3; range 65-928 cm3, n = 100) was significantly greater than that of the control group (101.4 cm3; range 36-171 cm3; n = 60; p = 0.00). The mean UA PI and RI values in the study group were significantly lower than their corresponding values in the control group (0.77 +/- 0.08 and 1.69 +/- 0.47 vs. 0.82 +/- 0.06 and 1.97 +/- 0.49, respectively, p = 0.01). When the myomatous uterine volumes of the study group were categorized into two subgroups (< 200 and > or = 200 cm2) the UA PI and RI values were lower in the latter group (p = 0.006 and p = 0.015, respectively). However, after analysis of receiver-operator-characteristic curves, none of the UA Doppler indices could differentiate the myomatous uterus from the normal uterus.