Samer Tannus

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.

Poor ovarian response as a predictor for live birth in older women undergoing IVF

Women of advanced age present a major challenge for fertility treatments. This study was designed to assess whether poor ovarian response (POR) according to the Bologna criteria is a significant predictor for live birth in women over 40. The outcomes of subsequent IVF cycles were also studied. The results of 1870 fresh IVF cycles in 1212 women were retrospectively analysed. The live birth per cycle was 3.3 times higher (11.61% versus 3.54%, P < 0.001) in good responders with more than three oocytes collected compared with women with less. Ovarian response defined by oocytes collected, but not by the number of follicles, was independently associated with live birth (odds ratio, 2.0; 95% confidence interval, 1.18 to 3.54; P = 0.009). The occurrence of POR in subsequent IVF cycles was only 55%. No differences in live births were found in persistent POR compared with women with at least one good response. A single episode of POR in a first IVF cycle in older women has a limited predictive value for the outcomes of subsequent cycles. POR in women aged 40-43 years, defined by the number of oocytes retrieved, is a predictor for live birth in IVF.

Oocyte in vitro maturation: A sytematic review

In vitro maturation (IVM) is one of the most controversial aspects of assisted reproductive technology. Although it has been studied extensively, it is still not a conventional treatment option and is accepted as an alternative treatment. However, studies have shown that IVM can be used in almost all areas where in vitro fertilization (IVF) is used and it has a strong place in fertility protection and Ovarian Hyperstimulation syndrome management. The aim of this systematic review was to address all aspects of the current knowledge of IVM treatment together with the evolution of IVM and IVF.

Decreased pregnancy and live birth rates after vitrification of in vitro matured oocytes

PurposeTo assess effects on fertilization rate, embryo quality, pregnancy, and live birth rates of vitrification and warming of oocytes that matured in vitro (vIVM) compared to fresh in vitro maturation (fIVM) cycles.MethodsA retrospective cohort study conducted at a university hospital-affiliated IVF unit. Fifty-six cycles of vIVM cycles and 263 fIVM in women diagnosed with polycystic ovarian syndrome (PCOS) ovaries were included in the analysis. The study group included PCOS patients who failed ovulation induction with intrauterine insemination and were offered IVM cycle followed by oocyte vitrification and warming. The embryological aspects and clinical outcomes were compared to those of controls undergoing fresh IVM cycles during the same period. The main outcome measure was live birth rate.ResultsOne thousand seventy oocytes were collected from 56 patients and underwent vitrification and warming. In the control group, 4781 oocytes were collected from 219 patients who had undergone a fresh IVM cycle. Oocyte maturation rates were similar between the groups (mean ± SD: 0.7 ± 0.2 vs. 0.6 ± 0.2, for vIVM and fIVM, respectively). Survival rate after warming was 59.8%. Fertilization and embryo cleavage rates per oocyte were significantly lower in the vIVM group. Clinical pregnancy (10.7 vs. 36.1%) and live birth rates (8.9 vs. 25.9%) per cycle were significantly lower in the vIVM group than those in the fIVM group (P = 0.005 and P < 0.001, respectively). Five healthy babies were born in the vIVM group.ConclusionsThe reproductive potential of vitrified IVM oocytes is impaired. This injury likely occurs through vitrification and warming.

Issues related to human oocyte vitrification: a consideration of the facts

Dear Editor, The advent of human oocyte vitrification has resulted in improved oocyte survival and reproductive potential that are equivalent to those of fresh retrieved oocytes. This has led the American Society for Reproductive Medicine (ASRM) in 2013 to change its position and classify oocyte cryopreservation as a non-experimental technique [1]. However, this change in position relied mainly on small-scale trials that came from the most experienced reproductive centers. Indeed, the ASRM had emphasized this fact and questioned whether the results of these trials can be generalized and reproduced in other fertility centers. However, since this change in committee position, there has been an increase in cycles that utilize vitrified oocytes, for the purpose of generating commercial banks of donor oocytes and for fertility preservation [2]. Although limited data is available on the outcomes of these cycles, the recent results show a persistently worse outcomes when using vitrified compared to fresh oocytes [3]. These worrisome results are particularly relevant to women who cryopreserve oocytes for social or medical reasons, for whom, this maybe their only hope to have their biologic offspring. This highlights the need of reproductive centers offering fertility preservation for continuous surveillance of the laboratory techniques to ensure consistent results. The following case can be an example of this issue. A 36-year-old healthy woman underwent three consecutive fertility preservation cycles which yielded a total of 43 MII oocytes that were vitrified. The oocytes from the first and second cycles (14 and 12 oocytes respectively) were vitrified by two senior embryologists and the oocytes from the third cycle (17 oocytes) were vitrified by a junior embryologist. Seven years later, at the age of 43, the patient returned for fresh IVF cycle with a partner. The patient opted also for oocytes thawing and fertilization. All the oocytes were thawed on the same day by the same embryologist. There was a significant difference in the oocyte survival rate between the three groups of oocytes: 71.4% (10/14) and 70.5% (12/17) for the first and third cycle, and 16.7% (2/12) for the second cycle (p = 0.04). These resulted in the formation of 18 embryos; of these, 8 were found to be euploid when tested by comparative genomic hybridization (CGH). Furthermore, four embryos were obtained from the fresh cycle; however, all were aneuploid when tested by CGH. Two embryos were transferred on day 5; however, pregnancy was not achieved. Three important points can be drawn from this case. First, as expected, oocyte vitrification for social fertility preservation is a way to obtain euploid embryos for use at an advanced age, when oocyte aneuploidy rate is high. This is not surprising, but has been minimally demonstrated. Secondly, oocytes can be vitrified for long periods (7 years in this case) and yet can survive, fertilize, and result in the formation of euploid embryos. The third point is that slight intra-laboratory variations in vitrification technique can result in different oocyte survival rates, even when performed under the same laboratory protocol. A recent study that analyzed the outcomes of oocyte donation cycles in the USA showed that between the years 2013 and 2015, there was a 44% increase in the utilization of vitrified oocytes along with a 33% decrease in the use of fresh oocytes [4]. However, cycle cancelation rates in vitrifiedthawed oocytes cycles increased from 8.5 to 15% compared to a decrease from 11.7 to 9.1% in cycles that used fresh oocytes between these years. This increase in cycle cancelation among vitrified oocyte cycles is likely related to lower oocyte survival rate and a lack of viable embryos to transfer. Furthermore, the live birth rate per recipient cycle start was * Samer Tannus sr.tannus@gmail.com

Combined modalities for the prevention of ovarian hyperstimulation syndrome following an excessive response to stimulation

Abstract Although the classification and management of ovarian hyperstimulation syndrome (OHSS) are well described in the literature, little attention has been given to modalities that aim to prevent its occurrence. In this retrospective study, we sought to investigate whether a combination of modalities in addition to GnRH agonist triggering in GnRH antagonist cycles could result in better prevention of OHSS. The study included 170 hyperresponder patients who were stimulated with GnRH antagonist protocol and were triggered with GnRH agonist for final oocyte maturation. Freeze all embryos was performed in all patients. The intervention group included treatment with dopamine agonist and restarting the GnRH antagonist. Of the 170 patients included, 63 were included in the intervention group. Compared to no intervention, women in the intervention group were more likely to have: menses within 7 days of the oocyte retrieval, smaller ovarian diameter, the absence of free pelvic fluid, less hemoconcentration and higher serum sodium levels. It can be concluded that combining other modalities in addition to triggering with GnRH agonist in GnRH antagonist cycles, results in targeting several pathways that lead to OHSS and result in rapid resolution of signs of ovarian hyperstimulation.

The effect of unilateral tubal block diagnosed by hysterosalpingogram on clinical pregnancy rate in intrauterine insemination cycles: systematic review and meta‐analysis

Fallopian tube occlusion is a common cause of infertility, but the effect of unilateral tubal block (UTB) on pregnancy rates (PR) after controlled ovarian hyperstimulation and intrauterine insemination (COH‐IUI) remains controversial.