T. Shavit

The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age

STUDY QUESTION Does ICSI improve reproductive outcomes compared with conventional IVF when used for non-male factor infertility in women aged 40 years and over? SUMMARY ANSWER There is no advantage of ICSI over conventional IVF in women aged 40 years and over when used for non-male factor infertility. WHAT IS KNOWN ALREADY The use of ICSI has increased dramatically in recent years and is being applied for indications other than male factor infertility. Currently, ICSI is used in 65% of IVF cycles in Europe and in 76% of cycles in the USA. Despite its increase use, there is no clear evidence of a benefit in using ICSI over conventional IVF. Older women undergoing infertility treatments are at an increased risk of having diminished ovarian reserve and lower oocyte quality, which could make ICSI the preferred insemination method in this group. However, studies that have examined the benefits of ICSI in this age group are lacking. STUDY DESIGN, SIZE, DURATION A retrospective, single center study included women, aged 40–43 years, who underwent IVF treatments for non-male factor infertility between January 2012 until June 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 745 women were included in the study. Of these, 490 women underwent ICSI and 255 women underwent conventional IVF. In order to be included in the study, women had to be at least 40 years of age at the beginning of ovarian stimulation and their male partner had to have normal sperm parameters according to World Health Organisation (WHO) fifth edition. Exclusion criteria included: more than three previous IVF cycles, a history of fertilization failure or low fertilization (<50%), the use of donor or frozen oocytes and the use of donor or frozen sperm samples. The primary outcome was the live birth rate. Secondary outcomes included fertilization rates, fertilization failure and embryo quality. MAIN RESULTS AND THE ROLE OF CHANCE Baseline characteristics were similar between the two groups, except for the number of previous IVF cycles, which was higher in the ICSI group (1.0 vs. 0.6, P = 0.0001). Despite similar numbers of oocytes retrieved (7.2 vs. 6.5), when examining oocytes maturity (performed 2 h after oocyte retrieval in the ICSI group and after 18 h in the conventional IVF group), the conventional IVF group had a higher number of Metaphase II (MII) oocytes (6.1 vs. 4.7, P < 0.0001). The conventional IVF group also had higher numbers of zygotes formed (4.48 vs. 3.66, P = 0.001), more cycles with embryos transferred at the blastocyst stage (36 vs. 26%, P = 0.005) and more cycles where embryos were available for cryopreservation (26.4 vs. 19.7%, P = 0.048), compared with the ICSI group. The fertilization rates (64 vs. 67%) and fertilization failure (9.0 vs. 9.7%) were similar. After logistic regression analysis controlling for confounders, the live birth rates were similar between the groups (11.9 vs. 9.6%). Subgroup analyses of women undergoing their first IVF cycle and women with ⩽3 oocytes retrieved did not show an advantage of ICSI over conventional IVF. LIMITATIONS, REASONS FOR CAUTION The retrospective nature of this study was a major limitation. The ICSI group had a higher number of previous IVF cycles, which could mean that ICSI was performed in poorer prognosis patients. Moreover, although this study is one of the largest studies to examine the question of whether ICSI is of value for older women with non-male factor infertility, based on a post hoc power analysis, it was still underpowered to detect differences in live birth rates, which can limit the conclusions of the study. Prospective studies are needed to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS The decision regarding performing ICSI should be based on sperm parameters and previous history. The use of ICSI for the sole indication of advanced maternal age shows no benefit over conventional IVF. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer

Possible differences between serum HCG levels in pregnancies achieved after transfer of a single fresh or a vitrified-warmed blastocyst were evaluated. Out of 1130 single blastocyst transfers resulting in positive HCG results, 789 were single fresh blastocyst transfers and 341 single vitrified-warmed blastocyst transfers. The initial serum HCG levels of 869 clinical intrauterine pregnancies were evaluated, 638 after the transfer of a single fresh blastocysts and 231 after the transfer of a single vitrified-warmed blastocysts. The HCG levels from cycles resulting in a clinical intrauterine pregnancy were significantly higher after the transfer of a single vitrified-warmed blastocyst (383 ± 230 IU/l) versus a fresh transfer (334 ± 192 IU/l; P = 0.01). Threshold values for predicting a clinical pregnancy for a fresh blastocyst were 111 IU/l and for a vitrified-warmed blastocyst 137 IU/l. Our study shows that the overall beta-HCG levels are comparable after the transfer of a fresh or vitrified-warmed blastocyst, suggesting that vitrification most probably does not affect the ability of the embryos to produce beta-HCG. This study further shows that when clinicians counsel patients, they should take into account that higher HCG levels are needed after a vitrified-warmed blastocyst transfer to predict a clinical intrauterine pregnancy.

Vitrified-warmed single-embryo transfers may be associated with increased maternal complications compared with fresh single-embryo transfers

Cryopreservation of embryos allows single-embryo transfer and storage of supernumerary embryos, maximizing cumulative pregnancy rates. The purpose of this retrospective cohort study was to compare pregnancy outcome in singletons born after fresh or vitrified-warmed single blastocyst transfer (SBT). Singleton live births resulting from SBT of fresh or vitrified-warmed embryos were compared. Primary outcomes were perinatal outcomes including small for gestational age (SGA), low birthweight, preterm deliveries (PTD), large for gestational age (LGA) and congenital malformations. Maternal complications included pre-eclampsia, placenta previa, placental abruption, gestational diabetes mellitus (GDM) and chorioamnionitis. Adjustment for confounding factors was performed. Of 1886 fresh SBTs and 1200 vitrified-warmed SBTs during the study period, vitrified-warmed SBTs compared with fresh SBTs resulted in significantly lower clinical pregnancy rate (P < 0.0001). Live birth and miscarriage rates calculated only for pregnancy with known outcome revealed lower live birth rates and higher miscarriage rates for the vitrified-warmed group. Perinatal complications were calculated for clinical pregnancies with known outcomes (12.9% catchment failure was excluded from analysis). The vitrified-warmed group showed a trend toward higher rates of pre-eclampsia, GDM, Caesarean delivery and LGA neonates. Rates of PTD and SGA were comparable. In conclusion, vitrified-warmed SBT might be associated with increased feto-maternal complications.

Quality of life of immigrant and non-immigrant infertile patients in a publicly funded in vitro fertilisation program: a cross-sectional study

To investigate whether there are differences in fertility quality of life (FertiQoL) and socio‐demographic characteristics between immigrants and non‐immigrant patients attending a government‐funded fertility program.

Oocyte Donation From Donor Older Than 35 Years. Is It Worth Trying

Introduction: Due to several reasons, in some countries commercial oocyte donation is not possible. Accordingly, patients should find their own donors who may be over 35 years. The aim of this study was to compare the results of oocyte donation from donors <35 years (young donors) and donors ≥35 years old (older donors). Material and Methods: A retrospective cohort study was conducted at a single academic reproductive center. We compared the results of oocyte donation from donors <35 years (345 cycles) and from donor ≥35 years old (83 cycles). We also performed subgroup analysis for single embryo transfer (SET) and fresh and frozen embryo transfers. Results: Recipient demographic characteristics of the 2 groups were comparable. The age of the donors was 29.8 ± 3.9 years in the young donor group and 37.6 ± 2.1 years in the older donor group (P < .0001). Pregnancy and implantation rates in the recipients from young donor group were statistically significantly higher than those from the older donor group (50.7% and 40.9% vs 38.3% and 23%; P = .04, P < .001). Cumulative pregnancy and live birth rates were significantly higher in the young donor group compared to the older donor group (86.1% vs 57.4% P < .0001 and 52.2% vs 33.3%, P = .02, respectively). Subgroup analysis showed comparable pregnancy and live birth rates for SET cycles (45.5% vs 40.4% and 25.0% vs 21.2%, respectively) and fresh cycles (54.7% vs 42.6% and 35.8% vs 29.6%, respectively). Conclusion: In nonanonymous oocyte donation programs, donation from older donors with good ovarian reserve is an acceptable approach when young donor is not available.

Infertility and Subfertility Cofactors in Women with PCOS

Infertility is defined as a failure to conceive after 12 months of unprotected intercourse. Due to the declining fertility with increasing age, couples in which the female partner age is older than 35 years may be considered as infertile after 6 months of unprotected intercourse. Irrespectively from a previous diagnosis of PCOS, the evaluation of infertility should focus on the couple and not solely on the female partner. In fact, even if one of the main cause of infertility include ovulatory dysfunction, some couples may be affected by tubal and uterine factors, endometriosis, male factor, and unexplained infertility. Infertility investigation is usually performed after a year of infertility, although earlier evaluation should be offered to those with known conditions related to subfertility. In women with PCOS, the main contributing factor for the infertility is anovulation, but several additional factors may play a role. This chapter discusses factors leading to anovulation in women with PCOS and additional characteristics of PCOS women that may affect their fertility potential.