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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: My Duc Hospital and Merck Sharp and Dohme.

The effect of intra-ovarian androgen priming on ovarian reserve parameters in Bologna poor responders.

RESEARCH QUESTION: What are the effects of long-term androgen priming in Bologna criteria poor ovarian reserve (POR) patients undergoing IVF? DESIGN: This open-label pilot study was conducted at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. It included consecutive patients aged 18-41 years who fulfilled Bologna criteria for POR undergoing intra-ovarian androgen priming and ultra-long down-regulation with a gonadotrophin-releasing hormone agonist (GnRHa), followed by stimulation with gonadotrophins and GnRH antagonist co-treatment for IVF (n = 30). Priming consisted of low-dose recombinant human chorionic gonadotrophin (rHCG) 260 IU every second day plus letrozole 2.5 mg/day, both for 8 weeks; priming stopped on the first day of ovarian stimulation. The primary endpoint was serum anti-Müllerian hormone (AMH) concentration 8 weeks after priming. Secondary endpoints included antral follicle count (AFC) (2-10 mm), serum human chorionic gonadotrophin (HCG), testosterone and progesterone levels. RESULTS: Circulating testosterone, progesterone, oestradiol and HCG levels remained unchanged during androgen priming; the mean AMH level decreased steadily from 0.49 ng/ml (baseline) to 0.33 ng/ml (8 weeks). AFC was 4-5 throughout the study. A mean of 1.1 ± 0.9 good transferable embryos were obtained; embryo transfer was performed in 15 patients; no ongoing pregnancies were obtained. CONCLUSIONS: Long-term intra-ovarian androgen priming in the current set-up had no significant effect on hormone levels, AFC and recruitable follicles after ovarian stimulation in Bologna POR patients undergoing IVF. Further studies are needed to explore other androgen priming protocols and the clinical value of priming regimens in IVF.