How successful is intrauterine insemination after failed IVF? A study of 551 women.

RESEARCH QUESTION: What is the success rate of intrauterine insemination (IUI) after failing IVF? DESIGN: This retrospective cohort study evaluated the pregnancy outcomes of 551 patients who underwent a total of 992 IUI cycles at an academic fertility centre between October 2008 and April 2018. RESULTS: The study participants (n = 551) had previously failed one to three fresh IVF cycles and any resultant embryo transfers, and subsequently underwent a total of 992 IUI cycles. When comparing demographics, women with ongoing pregnancies, clinical pregnancies and positive pregnancies were significantly younger (P = 0.037, P = 0.025 and P = 0.049, respectively) compared with women who did not conceive. The cumulative ongoing pregnancy rate for all IUI cycles was 7.44% per patient (41 pregnancies in 551 patients), and the ongoing pregnancy rate after the first IUI cycle was 4.72%. In single women who had previously failed six IUI cycles before undergoing IVF cycles with donor sperm, the cumulative ongoing pregnancy rate was 15.8% in donor sperm IUI cycles compared with 5.1% in women who used their partner's sperm for both IVF and IUI cycles, with an adjusted odds ratio of 6.1. Patient age, number of previous pregnancies, daily gonadotrophin dose for IVF, number of mature follicles at trigger, and number of failed IVF cycles failed to predict pregnancy outcomes. CONCLUSION: Ongoing pregnancy following IUI after failed IVF occurs at a rate of approximately 5% per cycle, and this rate is higher if donor sperm is used for both IVF and IUI cycles. This can be considered with proper counselling in women aged <40 years, and may be discouraged in women aged ≥43 years.

Successful pregnancy with restorative reproductive medicine after 16 years of infertility, three recurrent miscarriages, and eight unsuccessful embryo transfers with in vitro fertilization/intracytoplasmic sperm injection: a case report.

BACKGROUND: Restorative reproductive medicine represents a comprehensive approach to subfertility (infertility and miscarriage) with investigations, diagnoses, and treatments combined with fertility charting to restore optimal reproductive function. Restorative reproductive medicine assumes that multiple factors need to be identified and treated (cycle optimization) for up to 12 cycles to achieve a successful pregnancy. Conception can occur during normal intercourse without intrauterine insemination or in vitro fertilization. CASE PRESENTATION: A 35-year-old Croatian female presented for fertility treatment in May 2019 with a previous diagnosis of polycystic ovaries, infertility of 16 years duration, and 8 unsuccessful embryo transfers with in vitro fertilization and intracytoplasmic sperm injection. She was gravida 3 para 0, with 2 miscarriages after spontaneous conception at 5-6 weeks gestation in 2002 and 2004, followed by a miscarriage after in vitro fertilization at 12 weeks gestation in 2011. We initially found poor follicle function and suboptimal progesterone levels. Restorative reproductive medicine treatment resulted in conception after two cycles of treatment. This pregnancy ended in miscarriage at 7 weeks 4 days. Additional investigations found a balanced Robertsonian translocation (13, 14) and a uterine septum. We achieved repeat fertilization with restorative reproductive medicine after three cycles of treatment following resection of the uterine septum and ovulation induction with letrozole and human chorionic gonadotrophin. She had a full-term healthy pregnancy and live birth in 2021. CONCLUSION: We propose that a full evaluation of underlying factors, and up to 12 cycles of cycle optimization, should be offered to subfertile patients before considering in vitro fertilization treatment.

Effect of melatonin on the clinical outcome of patients with repeated cycles after failed cycles of in vitro fertilization and intracytoplasmic sperm injection.

To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10-11, 10-9, 10-7 and 10-5 M MT medium respectively, and 10-9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10-9 M MT, these 140 MT culture cycles were designated as the experimental group (10-9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10-9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10-9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10-9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.Trial registration: ChiCTR2100045552.

Elevated Levels of Serum Vascular Endothelial Growth Factor-A Are Not Related to NK Cell Parameters in Recurrent IVF Failure.

BACKGROUND: Vascular Endothelial Growth Factor and NK cells have an interrelated role in angiogenesis that is critical for placentation and success of in vitro fertilization. An attempt was made to assess a possible relationship between the two in this study. METHODS: A case control study was performed comparing the serum levels of VEGF-A and its receptor VEGF-R1 with levels of NK cells, activated NK cells and NK cytotoxicity in 62 women with Repeated Implantation Failure (RIF). The healthy control group consisted of 72 women of similar age, without known issues in achieving pregnancy or evidence of autoimmunity. Levels of VEGF-A and VEGF-R1 were quantified by ELISA methods with standard curve interpolation. NK cell subsets were determined with flow cytometry using fluorescent-tagged anti-CD56, anti-CD16, anti-CD3 and anti-CD69. NK cytotoxicity was performed by incubating peripheral blood mononuclear cells and K562 cultured cells with propidium iodide, steroid, intralipid and intravenous immunoglobulin, using previously described methods. Statistical analysis involved Mann-Whitney-U and Spearman's rank correlation testing with p-values defined as <0.05. RESULTS: It was found that VEGF-A levels were significantly raised in women with RIF compared to healthy controls (362.9 vs. 171.6 pg/ml, p<0.0001), with no difference in VEGF-R1 levels between groups (1499 vs. 1202 pg/ml, p=0.4082). There was no correlation between VEGF-A or VEGF-R1 and the absolute levels of circulating NK cells, CD69 activated NK cells or NK cytotoxicity. CONCLUSION: The absence of correlation between VEGF-A or VEGF-R1 and NK cells suggests VEGF secretion and regulation is independent of NK cell activity in RIF.