Conventional IVF Research Articles

More blastocysts are produced from fewer oocytes in ICSI\xa0 compared to IVF \u2013 results from a sibling oocytes study and definition of a new key performance indicator

BackgroundWhich fertilization method, between ICSI and IVF in split insemination treatments, has the highest clinical efficiency in producing clinically usable blastocyst?Methods211 infertile couples underwent split insemination treatments for a non-severe male factor. 1300 metaphase II (MII) oocytes were inseminated by conventional IVF and 1302 MII oocytes were micro-injected with the same partner’s semen. Embryo development until blastocyst stage on day V and clinical outcomes were valuated trough conventional key performance indicators (KPI), and new KPIs such as blastocyst rate per used MII oocytes and the number of MII oocytes to produce one clinically usable blastocyst from ICSI and IVF procedures.ResultsThe results were globally analyzed and according to ovarian stimulation protocol, infertility indication, and female age. The conventional KPI were online with the expected values from consensus references. From global results, 2.3 MII oocyte was needed to produce one clinically usable blastocyst after ICSI compared to 2.9 MII oocytes in IVF. On the same way, more blastocysts for clinical use were produced from fewer MII oocytes in ICSI compared to IVF in all sub-groups.ConclusionsIn split insemination treatments, the yield of clinically usable blastocysts was always superior in ICSI compared to IVF. The new KPI "number of needed oocytes to produce one clinically usable embryo" tests the clinical efficiency of the IVF laboratory.

Outcome of In-Vitro Fertilization in the First Government Set-up Fertility Center of Bangladesh

Introduction: Infertility as a global health issue is very much attended by the health sectors of most of the developed countries of the world. It remains as a neglected issue in Bangladesh’s reproductive health policy as emphasis is always been on the problem of overpopulation. Bangladesh Armed Forces have come forward to establish the first government set-up Artificial Reproductive Technology (ART) center to help the infertile couples of Bangladesh. Aim: To assess the outcome of in-vitro fertilization (IVF) procedures in relation to different demographic characteristics of the patients getting treatment at Fertility center, combined military hospital (CMH), Dhaka. Methods: Out of more than thousand patients, 46 couples were selected for IVF cycle scheduled to be held on the month of July 2017 and October 2017. Each selected female and male patient had a normal basic fertility work up. In both batches, female factors were predominant. Male factor and combined factors were also present. Data were collected prospectively using a data collection sheet over the period of one year starting from July 2017 to June 2018 to observe the last patient upto the delivery of her offspring. Results: A total of 46 couples or 92 patients were treated for infertility. Out of 46 female patients, most (about 40%) were within the range of 26 to 30 years of age. About two-thirds patients had primary subfertility. Most common cause of infertility of female partners was the tubal cause (52%) and of male partners was severe oligozoospermia (47%). A procedure of IVF like conventional IVF was done in 64% and Intra Cytoplasmic Sperm Injection (ICSI) in the remaining. Embryo transfer was performed in 30 patients. The embryos of 13 (33%) patients were cryopreserved in both batches. Rate of retrieved oocytes ranged from 3 to 29 in the 1st batch and for the 2nd batch it was from 1 to 17. Pregnancy rate was 80% in first batch, but in the second batch it was only 33%. Abortion rate was also very high (80%) in the second batch. Conclusion: In fact, infertility has become a burning health issue to the sufferers of fertility problems as well as career-oriented generation of this century and the society seeks the remedy to help them. Like the Fertility Center, CMH, Dhaka other government set up centers should come up to provide facilities that enables the women having the dream of motherhood true. JAFMC Bangladesh. Vol 15, No 1 (June) 2020: 29-34

Obstetrical and Neonatal Outcomes of 3,028 Singletons Born After Advanced ART Techniques: Ejaculated Sperm Intracytoplasmic Sperm Injection, Artificial Oocyte Activation, in Vitro Maturation and Testicular Sperm Extraction

Background: To evaluate obstetrical and neonatal outcomes of singletons conceived after advanced assisted reproductive technology (ART) techniques: conventional IVF pregnancies (C-IVF), ejaculated sperm intracytoplasmic sperm injection (ICSI), assisted oocyte activation (AOA), in vitro maturation (IVM), and testicular sperm extraction (TESE). Methods: The subjects were 3,028 singletons who were born after fresh or frozen embryo transfer. The subjects were separated into five groups: C-IVF ([Formula: see text]), ICSI ([Formula: see text]), AOA ([Formula: see text]), IVM ([Formula: see text]), and TESE ([Formula: see text]). We evaluated obstetrical and neonatal outcomes calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses for fresh and frozen embryos and for cleavage and blastocyst transfer. The C-IVF group was used as a background control for the ICSI group. Moreover, the TESE, AOA, and IVM groups were compared to the ICSI group to evaluate the effects of the ICSI procedure itself. Results: The incidence of perinatal complications was significantly lower in the ICSI-fresh group ([Formula: see text], 95% CI: 0.10–0.83, [Formula: see text]). Regarding sex ratio, the IVM was significantly associated with sex ratio imbalance toward female in both fresh and frozen groups ([Formula: see text], 95% CI: 0.10–0.96, [Formula: see text], 95% CI: 0.07–0.98, [Formula: see text]). On the other hand, there were no significant differences in preterm birth rate, low birth weight rate and congenital abnormalities rate between conventional IVF, ICSI, and the other groups. Conclusions: There were no negative effects on obstetrical and neonatal outcomes between conventional IVF and ICSI. Although this was a limited sample size study, advanced ART technologies such as AOA, IVM, and TESE also seem to have a low risk of adverse impact on obstetrical and neonatal outcomes but may have a slight impact on sex ratio.

In vitro fertilisation (IVF) versus intracytoplasmic sperm injection (ICSI) in patients without severe male factor infertility: study protocol for the randomised, controlled, multicentre trial INVICSI

IntroductionOver the last decades, the use of intracytoplasmic sperm injection (ICSI) has increased, even among patients without male factor infertility. The increase has happened even though there is no evidence...

Genome stabilization by RAD51-stimulatory compound 1 enhances efficiency of somatic cell nuclear transfer-mediated reprogramming and full-term development of cloned mouse embryos.

ObjectivesThe genetic instability and DNA damage arise during transcription factor‐mediated reprogramming of somatic cells, and its efficiency may be reduced due to abnormal chromatin remodelling. The efficiency in somatic cell nuclear transfer (SCNT)‐mediated reprogramming is also very low, and it is caused by development arrest of most reconstituted embryos.Materials and MethodsWhether the repair of genetic instability or double‐strand breaks (DSBs) during SCNT reprogramming may play an important role in embryonic development, we observed and analysed the effect of Rad 51, a key modulator of DNA damage response (DDR) in SCNT‐derived embryos.ResultsHere, we observed that the activity of Rad 51 is lower in SCNT eggs than in conventional IVF and found a significantly lower level of DSBs in SCNT embryos during reprogramming. To address this difference, supplementation with RS‐1, an activator of Rad51, during the activation of SCNT embryos can increase RAD51 expression and DSB foci and thereby increased the efficiency of SCNT reprogramming. Through subsequent single‐cell RNA‐seq analysis, we observed the reactivation of a large number of genes that were not expressed in SCNT‐2‐cell embryos by the upregulation of DDR, which may be related to overcoming the developmental block. Additionally, there may be an independent pathway involving histone demethylase that can reduce reprograming‐resistance regions.ConclusionsThis technology can contribute to the production of comparable cell sources for regenerative medicine.

Single oral dose of vitamin D3 supplementation prior to in vitro fertilization and embryo transfer in normal weight women: the SUNDRO randomized controlled trial

Improving invitro fertilization success is an unmet need. Observational studies have suggested that women with deficient or insufficient vitamin D have lower chances of invitro fertilization success, but whether supplementation improves clinical pregnancy rate remains unclear. This study aimed to determine whether oral vitamin D3 supplementation improves clinical pregnancy in women undergoing an invitro fertilization cycle. The "supplementation of vitamin D and reproductive outcome" trial is a 2-center randomized superiority double-blind placebo-controlled trial. Subjects were recruited between October 2016 and January 2019. Participants were women aged 18 to 39 years with low vitamin D (peripheral 25-hydroxyvitamin D of <30 ng/mL), serum calcium of ≥10.6 mg/dL, body mass index of 18 to 25 kg/m2, and antimüllerian hormone levels of >0.5 ng/mL and starting their first, second, or third treatment cycle of conventional invitro fertilization or intracytoplasmic sperm injection. The primary outcome was the cumulative clinical pregnancy rate per cycle. Pregnancies obtained with both fresh or frozen embryo transfers were included. Clinical pregnancy was defined as an intrauterine gestational sac with a viable fetus. The primary analysis was performed according to the intention-to-treat principle and could also include natural conceptions. Secondary outcomes included total dose of gonadotropins used, embryologic variables (number of oocytes retrieved, number of suitable oocytes retrieved, fertilization rate, and rate of top-quality embryos), and clinical outcomes (miscarriage rate and live birth rate). Overall, 630 women were randomized 2 to 12 weeks before the initiation of the invitro fertilization cycle to receive either a single dose of 600,000 IU of vitamin D3 (n=308) or placebo (n=322). Interestingly, 113 (37%) and 130 (40%) women achieved a clinical pregnancy in the treatment and placebo groups, respectively (P=.37). The risk ratio of clinical pregnancy in women receiving vitamin D3 was 0.91 (95% confidence interval, 0.75-1.11). Compared with the placebo, vitamin D3 supplementation did not improve the rate of clinical pregnancy. Exploratory subgroup analyses for body mass index, age, indication to invitro fertilization, ovarian reserve, interval between drug administration and initiation of the cycle, and basal levels of 25-hydroxyvitamin D failed to highlight any clinical situation that could benefit from the supplementation. In women with normal weight with preserved ovarian reserve and low vitamin D levels undergoing invitro fertilization cycles, a single oral dose of 600,000 IU of vitamin D3 did not improve the rate of clinical pregnancy. Although the findings do not support the use of vitamin D3 supplementation to improve invitro fertilization success rates, further studies are required to rule out milder but potentially interesting benefits and explore the effectiveness of alternative modalities of supplementation.

Does Ovarian Endometriosis Increase Oocyte Sensitivity to ICSI-Induced Mechanical Damage?

Some studies have shown that ICSI obtains poorer results than conventional IVF in women with ovarian endometriosis, suggesting that oocytes could be sensitive to ICSI-induced mechanical damage. The aims of this study were to clarify (a) whether ovarian endometriosis could induce peculiar fragility in the oocyte, so that ICSI would finally result harmful, and (b) whether endometrioma removal before IVF could be advisable in order to avoid any hypothetical detrimental effect. We retrospectively studied 368 women, 203 with in situ endometrioma (128 of which underwent ICSI, 75 conventional IVF) and 164 who received laparoscopic stripping of endometrioma before ICSI. For women with in situ endometrioma, cIVF and ICSI outcome was comparable for all parameters studied, including the clinical pregnancy rate per embryo transfer (PR/ET: 31.8% vs. 39.5% in the cIVF and ICSI groups) and cumulative live birth rate per ovum pick-up (CLBR/OPU: 24.4% vs. 27.7%). ICSI outcome was similar comparing women with in situ endometrioma and women previously submitted to laparoscopic stripping of cysts (CLPR/OPU 27.7% vs. 25.3%). Our findings suggest that (a) in women with in situ endometrioma ICSI may be performed, when needed, without harming oocytes and compromising the outcome and (b) that there is no advantage in removing endometrioma before ICSI.

Role of Luteal Phase Endometrial Injury in Outcome of In Vitro Fertilization

ABSTRACT Introduction The development of receptive endometrium is necessary for successful implantation, which is now considered a rate-limiting step for the success of in vitro fertilization (IVF). Lately, scratching of endometrium before embryo transfer (ET) is being investigated as a possible technique to increase implantation rate. By improving endometrial receptivity, the endometrial injury might increase implantation and clinical pregnancy rates. Materials and methods A total of 100 patients, who met the inclusion criteria, were randomized into two groups, group I (study group) in which endometrial scratching was done before ET, and group II (control group) in which endometrial scratching was not done. All the patients had previous history of implantation failure at one or more occasions. Results In group I, 19/35 patients who underwent IVF conceived whereas in group II, 9/30 patients conceived. The conception rate in intervention group was higher than the control group for patients who underwent conventional IVF and this difference was found to be statistically significant, p value 0.049. In group I, 29 (58.0%) babies were born to 50 women who underwent intervention and in group II, 15 babies were born. This difference in carry-home baby rate was statistically significant (p = 0.005). Conclusion The benefit of luteal phase endometrial injury cannot be refuted and larger multicenter randomized controlled trials are required for conclusive evidence. How to cite this article Kriplani I, Garg S, Goel P, et al. Role of Luteal Phase Endometrial Injury in Outcome of In Vitro Fertilization. J Mahatma Gandhi Univ Med Sci Tech 2020;5(2):47–49.

Thyroid function modifications in women undergoing controlled ovarian hyperstimulation for in vitro fertilization: a systematic review and meta-analysis

To investigate the impact of controlled ovarian hyperstimulation (COH) for invitro fertilization (IVF) on thyroid function. Systematic review and meta-analysis. Not applicable. Infertile women undergoing conventional IVF or intracytoplasmic sperm injection. Systematic search of PubMed, MEDLINE, Embase, Scopus, and Web of Science from inception until November 2020. Studies could be included only if they met the following criteria: subjects were classified as euthyroid or hypothyroid; serum thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) levels were evaluated before COH; and the same thyroid function test was reassessed after COH (i.e., at the time of trigger for final follicle maturation and/or at pregnancy test). Mean difference (MD) between the serum TSH or FT4 levels assessed after COH and before COH. In euthyroid women, the serum TSH levels assessed at the time of trigger and at the time of pregnancy test were significantly higher than those at baseline (MD: 0.69 mIU/L, 95% confidence interval [CI]: 0.30-1.08, I2 = 93% and MD: 0.67, 95% CI: 0.49-0.85, I2 = 72%, respectively). The serum FT4 levels did not undergo significant changes. Subanalysis confirmed an increase in the TSH level after restricting the analysis to women treated with gonadotropin-releasing hormone agonist protocols and to those who achieved pregnancy. A pronounced increase in the TSH level was observed in women treated for hypothyroidism (MD: 1.50 mIU/L, 95% CI: 1.10-1.89, I2 = 0%). Pooling of the results showed a significant increase in serum TSH level in women undergoing COH for IVF. This change was particularly pronounced in women treated for hypothyroidism. New thyroid function screening strategies for women undergoing COH are warranted.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial

The use of intracytoplasmic sperm injection has increased substantially worldwide, primarily in couples with non-male factor infertility. However, there is a paucity of evidence from randomised trials supporting this approach compared with conventional in-vitro fertilisation (IVF). We aimed to investigate whether intracytoplasmic sperm injection would result in a higher livebirth rate compared with conventional IVF. This open-label, multicentre, randomised trial was done at two IVF centres in Ho Chi Minh City, Vietnam (IVFMD, My Duc Hospital and IVFAS, An Sinh Hospital). Eligible couples were aged at least 18 years and the male partner's sperm count and motility (progressive motility) were normal based on WHO 2010 criteria. Couples had to have undergone two or fewer previous conventional IVF or intracytoplasmic sperm injection attempts, have used an antagonist protocol for ovarian stimulation, and agree to have two or fewer embryos transferred. Couples were randomly assigned (1:1) to undergo either intracytoplasmic sperm injection or conventional IVF, using block randomisation with variable block size of 2, 4, or 8 and a telephone-based central randomisation method. The computer-generated randomisation list was prepared by an independent statistician who had no other involvement in the study. Embryologists and couples were not masked to study groups because of the type of interventions and differences in hospital fees, but clinicians performing embryo transfer were unaware of study group allocation. The primary outcome was livebirth after the first embryo transfer from the initiated cycle. Analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03428919. Between March 16, 2018, and Aug 12, 2019, we randomly assigned 1064 couples to intracytoplasmic sperm injection (n=532) or conventional IVF (n=532). Livebirth after the first embryo transfer from the initiated cycle occurred in 184 (35%) of 532 couples randomly assigned to intracytoplasmic sperm injection and in 166 (31%) of 532 couples randomly assigned to conventional IVF (absolute difference 3·4%, 95% CI -2·4 to 9·2; risk ratio [RR] 1·11, 95% CI 0·93 to 1·32; p=0·27). 29 (5%) couples in the intracytoplasmic sperm injection group and 34 (6%) couples in the conventional IVF group had fertilisation failure (absolute difference -0·9%, -4·0 to 2·1, RR 0·85, 95% CI 0·53 to 1·38; p=0·60). In couples with infertility in whom the male partner has a normal total sperm count and motility, intracytoplasmic sperm injection did not improve the livebirth rate compared with conventional IVF. Our results challenge the value of the routine use of intracytoplasmic sperm injection in assisted reproduction techniques for this population. My Duc Hospital and Merck Sharp and Dohme.

Intracytoplasmic sperm injection versus conventional IVF

Intracytoplasmic sperm injection is a widely used fertilisation method that involves injecting a single spermatozoon into oocyte cytoplasm using a glass micropipette.1 Although it was introduced as a modification of conventional in-vitro fertilisation (IVF) to overcome severe male factor infertility,2 intracytoplasmic sperm injection has become the most common laboratory technique in assisted reproductive technology, accounting for almost 70% of the around 2·8 million annual assisted reproductive technology cycles, according to global estimates.

Relationship between follicular size and developmental capacity of oocytes under controlled ovarian hyperstimulation in assisted reproductive technologies.

PurposeWe investigate the relationships between oocyte developmental capacity and follicular size of its origin in Japanese women: those undergoing conventional IVF (cIVF) and ICSI, respectively.MethodsA total of 3377 follicles were punctured separately and were classified into three groups (large, medium, and small) by their diameters. A total of 1482 retrieved oocytes were individually cultured and received cIVF or ICSI. The oocytes receiving ICSI were denuded and the number of mature (MII) oocytes was counted.ResultsThe oocyte retrieval rates and the proportion of MII oocytes were significantly lower in small follicles than in large follicles. Under cIVF, the fertilization rate was significantly lower in oocytes from small follicles than large follicles. Under ICSI, the fertilization rate for MII oocytes was not significantly related to follicular size. Follicular size was not significantly related to the development potential to blastocyst and pregnancy rate for either the cIVF oocytes or the ICSI oocytes.ConclusionsAlthough the fertilization rate by cIVF is low in oocytes from small follicles due to the lower proportion of mature oocytes, their development potential is comparable to that of oocytes from larger follicles if they could be fertilized. Under ICSI using mature oocytes, their development potential is not related to follicular size.

Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis.

The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta-analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE-PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI-NIH quality assessment tool was used to assess the quality of each study. Meta-analyses were conducted using the Mantel-Haenszel method with random-effects models to evaluate the Risk Ratio (RR) between high-DNA-damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I2 statistic. We also conducted sensitivity analyses and post-hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta-analysis, comprising 12380 IVF/ICSI cycles. Meta-analysis revealed that, considering IVF and ICSI results together, implantation rate (RR=0.74; 95% CI=0.61-0.91; I2 = 69) and pregnancy rate (RR=0.83; 0.73-0.94; I2 = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non-significant but detrimental tendency (RR=0.78; 0.58-1.06; I2 = 72) on live birth rate. Meta-analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR=0.68; 0.52-0.89; I2 = 50) and pregnancy rates (RR=0.72; 0.55-0.95; I2 = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR=0.48; 0.22-1.02; I2 = 79). In the case of ICSI, non-significant trends were observed for implantation (RR=0.79; 0.60-1.04; I2 = 72) or pregnancy rates (RR=0.89; 0.78-1.02; I2 = 44), and live birth rate (RR=0.92; 0.67-1.27; I2 = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well-designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.

ICSI Does Not Improve Live Birth Rates but Yields Higher Cancellation Rates Than Conventional IVF in Unexplained Infertility.

Objectives: Unexplained infertility has been one of the indications for utilization of intracytoplasmic sperm injection (ICSI). However, whether ICSI should be preferred to IVF for patients with unexplained infertility remains an open question. This study aims to determine if ICSI improves the clinical outcomes over conventional in vitro fertilization (IVF) in couples with unexplained infertility.Methods: This was a retrospective cohort study of 549 IVF and 241 ICSI cycles for patients with unexplained infertility at a fertility center of a university hospital from January 2016 and December 2018. The live birth rate and clinical pregnancy rate were compared between the two groups. Other outcome measures included the implantation rate, miscarriage rate, and fertilization rate.Results: The live birth rate was 35.2% (172/488) in the IVF group and 33.3% (65/195) in ICSI group, P = 0.635. The two groups also had similar clinical pregnancy rates, implantation rates, and miscarriage rates. The fertilization rate of IVF group was significantly higher than that of ICSI group (53.8 vs. 45.7%, P = 0.000, respectively). Sixty-one and 46 patients did not transfer fresh embryos in IVF and ICSI cycles, respectively. Patients with IVF cycles had lower cancellation rates than those with ICSI (11.1 vs. 19.1%, P = 0.003, respectively).Conclusion: ICSI does not improve live birth rates but yields higher cancellation rates than conventional IVF in the treatment of unexplained infertility.

Competence of embryos showing transient developmental arrest during in vitro culture.

In vitro developing embryos may apparently show no developmental progress during 24 h and resume their development up to the blastocyst stage. The present study was conducted to assess their ability to implant and to give rise to a live birth when replaced at day 5 (fresh or vitrified/warmed) as compared to continuously developing embryos. Embryo development follow-up and grade were prospectively recorded in a photo database. The studied period was from April 2011 to July 2017. The studied embryos included transient arrested embryos (TAE) that showed the same developmental stage at two subsequent observations, i.e. between day 2 and day 3 (d2 and d3), between day 3 and day 4 (d3 and d4) and between day 4 and day 5 (d4 and d5). TAE were compared to continuously developing embryos (CDE). Elective day 5 embryo transfers were performed. Woman age was higher in TAE (34.3±3.9) than in CDE (32.9±4.8) (p<0.01). TAE were more frequently (63.1%) observed after ICSI than after conventional IVF (55.9%) (p<0.01). Implantation rate was reduced in TAE as compared to CDE, after both fresh (10.0% vs 23.8% [p<0.01]) and vitrified/warmed (12.9% vs 19.0% [p<0.01]) embryo transfers. Delivery rate was also lower after the transfer of fresh (8.3% vs 19.4% [p<0.01]) and vitrified/warmed (8.5% vs 14.1% [p<0.01]) TAE as compared to CDE. Implantation and delivery rates were not statistically different whether embryo arrested between day 2 and day 3 (d2 and d3), between day 3 and day 4 (d3 and d4) or between day 4 and day 5 (d4 and d5). TAE may be considered for transfer at a lower priority than CDE and associated with inferior prognosis than CDE.

Glucose metabolism characterization during mouse in vitro maturation identifies alterations in cumulus cells†.

In vitro maturation (IVM) is an assisted reproduction technique with reduced hormone-related side-effects. Several attempts to implement IVM in routine practice have failed, primarily due to its relatively low efficiency compared with conventional in vitro fertilization (IVF). Recently, capacitation (CAPA)-IVM-a novel two-step IVM method-has improved the embryology outcomes through synchronizing the oocyte nuclear and cytoplasmic maturation. However, the efficiency gap between CAPA-IVM and conventional IVF is still noticeable especially in the numerical production of good quality embryos. Considering the importance of glucose for oocyte competence, its metabolization is studied within both in vivo and CAPA-IVM matured mouse cumulus-oocyte-complexes (COCs) through direct measurements in both cellular compartments, from transcriptional and translational perspectives, to reveal metabolic shortcomings within the CAPA-IVM COCs. These results confirmed that within in vivo COC, cumulus cells (CCs) are highly glycolytic, whereas oocytes, with low glycolytic activity, are deviating their glucose towards pentose phosphate pathway. No significant differences were observed in the CAPA-IVM oocytes compared with their in vivo counterparts. However, their CCs exhibited a precocious increase of glycolytic activity during the pre-maturation culture step and activity was decreased during the IVM step. Here, specific alterations in mouse COC glucose metabolism due to CAPA-IVM culture were characterized using direct measurements for the first time. Present data show that, while CAPA-IVM CCs are able to utilize glucose, their ability to support oocytes during final maturation is impaired. Future CAPA-IVM optimization strategies could focus on adjusting culture media energy substrate concentrations and/or implementing co-culture strategies.

Fresh and cumulative live birth rates in mild versus conventional stimulation for IVF cycles in poor ovarian responders: a systematic review and meta-analysis.

Are cumulative and live birth rates (LBRs) comparable in poor ovarian response women treated with different protocols of mild stimulation IVF (i.e. oral compounds, lower doses or shorter treatments) versus conventional IVF? Mild ovarian stimulation (MOS) results in comparable outcomes to those of conventional stimulation in poor ovarian response patients with low ovarian reserve. Several randomized trials and meta-analyses have been published evaluating the role of mild (MOS) versus conventional ovarian stimulation in poor ovarian response patients. Most report a potentially higher safety profile, patient satisfaction and lower costs, suggesting that the higher cycle cancellation rate and fewer oocytes retrieved following MOS does not affect the final reproductive outcome. Additionally, over the last few years, new publications have added data regarding MOS, and shown the possible benefit of a higher oocyte yield which may also improve prognosis in patients with poor ovarian response. We conducted a systematic search of relevant randomized controlled trials (RCTs). We searched electronic databases, including MEDLINE, EMBASE, LILACS-BIREME, CINAHL, The Cochrane Library, CENTRAL (Cochrane Register), Web of Science, Scopus, Trip Database and Open Grey, to identify all relevant studies published up to March 2020. We examined trial registries for ongoing trials. No publication-year or language restrictions were adopted. We explored the reference list of all included studies, reviews and abstracts of major scientific meetings. The primary outcomes were cumulative and fresh LBR (CLBR and FLBR) per woman randomized. We included subfertile women undergoing IVF/ICSI characterized as poor responders and compared primary and secondary outcomes between the different protocols of mild stimulation IVF (i.e. oral compounds, lower doses or shorter treatments) and conventional IVF. We used the PICO (Patients, Intervention, Comparison and Outcomes) model to select our study population. Overall, 15 RCTs were included in the meta-analysis. CLBR and FLBR were comparable between mild versus conventional stimulation (RR 1.15; 95% CI: 0.73 - 1.81; I2 = 0%, n = 424, moderate certainty and RR 1.01; 95% CI: 0.97 - 1.04; I 2 = 0%, n = 1001, low certainty, respectively). No difference was observed either when utilizing oral compounds (i.e. letrozole and clomiphene) or lower doses. Similarly, ongoing pregnancy rate (OPR) and clinical pregnancy rate (CPR) were equivalent when comparing the two groups (RR 1.01; 95% CI: 0.98 - 1.05; I 2 = 0%, n = 1480, low certainty, and RR 1.00; 95% CI: 0.97 - 1.03; I2 = 0%, n = 2355, low certainty, respectively). A significantly lower oocyte yield (mean differences (MD) -0.80; 95% CI: -1.28, -0.32; I2 = 83%, n = 2516, very low certainty) and higher rate of cycle cancellation (RR 1.48; 95% CI: 1.08 - 2.02; I2 = 62%, n = 2588, low certainty) was observed in the MOS group. The overall quality of the included studies was low to moderate. Even though strict inclusion criteria were used, the selected studies were heterogeneous in population characteristics and treatment protocols. We found no differences in CLBR between MOS and COS (95% CI: 0.73 - 1.81.). MOS could be considered as a treatment option in low prognosis poor responder patients, given that it results in similar fresh and CLBRs compared with COS. A milder approach is associated with a lower number of oocytes retrieved and a higher cancellation rate, although treatment cost is significantly reduced. Future research should focus on which type of ovarian stimulation may be of benefit in better prognosis women. There were no sources of financial support. N.P.P. received research grants, honoraria for lectures from: Merck Serono, MSD, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex and Gedeon Richter. P.D. received unrestricted grants and honoraria from Merck Serono, MSD and Ferring Pharmaceuticals. I.G.F. received unrestricted grants and honoraria from Merck Serono, MSD, Ferring Pharmaceuticals, Gedeon-Richter and IBSA. P.M.B. reported no conflict of interest. CRD42020167260.

Machine-learning algorithm incorporating capacitated sperm intracellular pH predicts conventional in vitro fertilization success in normospermic patients

To measure human sperm intracellular pH (pHi) and develop a machine-learning algorithm to predict successful conventional invitro fertilization (IVF) in normospermic patients. Spermatozoa from 76 IVF patients were capacitated invitro. Flow cytometry was used to measure sperm pHi, and computer-assisted semen analysis was used to measure hyperactivated motility. A gradient-boosted machine-learning algorithm was trained on clinical data and sperm pHi and membrane potential from 58 patients to predict successful conventional IVF, defined as a fertilization ratio (number of fertilized oocytes [2 pronuclei]/number of mature oocytes) greater than 0.66. The algorithm was validated on an independent set of data from 18 patients. Academic medical center. Normospermic men undergoing IVF. Patients were excluded if they used frozen sperm, had known male factor infertility, or used intracytoplasmic sperm injection only. None. Successful conventional IVF. Sperm pHi positively correlated with hyperactivated motility and with conventional IVF ratio (n = 76) but not with intracytoplasmic sperm injection fertilization ratio (n = 38). In receiver operating curve analysis of data from the test set (n = 58), the machine-learning algorithm predicted successful conventional IVF with a mean accuracy of 0.72 (n = 18), a mean area under the curve of 0.81, a mean sensitivity of 0.65, and a mean specificity of 0.80. Sperm pHi correlates with conventional fertilization outcomes in normospermic patients undergoing IVF. A machine-learning algorithm can use clinical parameters and markers of capacitation to accurately predict successful fertilization in normospermic men undergoing conventional IVF.

Issues des transferts cumulés d’embryons frais et congelés en fécondation in vitro chez les femmes infectées par le virus de l’hépatite B

ObjectiveTo assess the impact of hepatitis B virus (HBV) infection in women on in vitro fertilization (IVF) outcomes. MethodsAn observational monocentric case-control cohort study conducted between 2012 and 2019 compared the outcomes of the first cycle of IVF between 64 woman infected with HBV and 128 seronegative controls. Frozen embryos transfers made within 18 months of the puncture were included. The exclusion criteria were severe infections, viral co-infection in women, any viral infection in their spouse, or lack of fresh embryo transfer. The matching was performed according to age, primary infertility or secondary, conventional or intracytoplasmic injection IVF technique and date of attempt. The main analysis focused on cumulative live births rates (LBR). ResultsThe clinical and ovarian stimulation characteristics were comparable except for a longer period of infertility in the HBV group. The LBR in the HBV group, when compared to controls, was not different after transfer of fresh (14.06 vs. 25.00% P=0.08) or frozen embryos (4.17 vs. 18.92% P=0.08), but significantly decreased in cumulative analysis (15.63 vs. 35.94% P=0.003). HBV infection was negatively associated with LBR in multivariate analysis OR=0.38 (95% CI 0.14–0.92) P<0.05. The implantation rate was lower in the HBV group versus controls, in fresh (14.89 vs. 27.72% P=0.02) and frozen (3.03 vs. 21.65% P=0.01) embryo transfers. ConclusionThis study suggests a negative impact of HBV infection in women on the cumulative LBR after IVF.

Effectivity of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) when male factor is absent: a perspective point of view.

An objective and individualized approach of in vitro fertilization techniques tends to decrease costs and improve the experience of infertile couples during treatment. The use of available technologies to diagnose and treat infertility based on scientific evidence seems to be the best practice, which is the guideline that motivates this review on the available techniques for laboratory oocyte insemination. Conventional IVF, the pioneering technique, was initially used in the treatment of tubal obstruction infertility, successfully expanding the treatment of infertile couples presenting with several other factors. However, it was less effective in cases of severe male factor infertility. Intracytoplasmic sperm injection, which was developed in 1992, proved to be the method of choice for treating couples with severe male factor infertility. Since then, it has been increasingly used regardless of the infertility factor. This review discusses the effectiveness of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) when the male factor is absent in all aspects, as technical and clinical outcomes, associated risks, adjustments for using with other technologies and costs. Finally we discuss the advantages and disadvantages of each one, with all aspects reviewed.