Intrauterine insemination + controlled ovarian hyperstimulation versus in vitro fertilisation in unexplained infertility: a systematic review and meta-analysis.

BACKGROUND: IUI + COH is widely used in cases of unexplained infertility before resorting to IVF. Debate continues about what should be the first-line treatment for couples with unexplained infertility. OBJECTIVES: This systematic review assessed the relative efficacy of IUI + COH compared with IVF in couples with unexplained infertility. SEARCH STRATEGY: We searched Medline, Embase, CIHNL, Pscy Info, and Cochrane Library from 1980 to November 2019. SELECTION CRITERIA: Only RCTs published articles in full text with female patients aged 18-43 years and diagnosed with unexplained infertility were included. DATA COLLECTION AND ANALYSIS: Two authors reviewed citations from primary search independently and any disagreement was resolved by mutual discussion and consultation with a third author. MAIN RESULT: In total, eight RCTs were included. The quality of evidence was moderate to low due to inconsistency across the trials and imprecision. The pooled result showed that IVF was associated with a statistically significant higher live birth rate (RR 1.53, 95% CI 1.01-2.32, P < 0.00001 I2 = 86%) with no significant difference in multiple pregnancy rate or OHSS rate. Sensitivity analysis based on women's age and a history of previous IUI or IVF treatment showed no significant difference in the live birth rates (RR 1.01, 95% CI 0.88-1.15, I2 = 0%, 3 RCTs) in treatment-naïve women younger than 38 years. In women over 38 years, the live birth rates were significantly higher in the IVF group (RR 2.15, 95% CI 1.16-4.0, I2 = 42%, 1 RCT). CONCLUSION: Further research using a standardised treatment protocol and taking into account important prognostic variables and cumulative live birth rates from fresh IVF and all sibling frozen embryos is required to further guide clinical practice.

Cumulative outcome of pre-implantation genetic diagnosis for sickle cell disease: a 5-year review.

To review the cumulative outcome of pre-implantation genetic diagnosis (PGD) cycles performed for prevention of sickle cell disease (SCD). Couples referred for PGD for SCD between April 2012 and October 2017 were included. Ovarian stimulation was performed using a short gonadotrophin-releasing hormone (GnRH) antagonist protocol and follicle-stimulating hormone injections. The GnRH agonist was used to trigger oocyte maturation. Oocytes were fertilised using intracytoplasmic sperm injection. Trophectoderm biopsy was performed on day 5 or 6 followed by vitrification. Genetic testing was done using pre-implantation genetic haplotyping. A total of 60 couples started 70 fresh PGD cycles (mean 1·2 cycles/couple) and underwent a total of 74 frozen-embryo-transfer (FET) cycles (mean 1·3 FET/couple). The mean (SD) female age was 33 (4·4) years and the mean (SD) anti-müllerian hormone level was 22·9 (2·8) pmol/l. The cumulative live-birth rate was 54%/PGD cycle started and 63%/couple embarking on PGD. The rate of multiple births was 8%. The cumulative outcome of PGD treatment for prevention of SCD transmission is high and PGD treatment should be offered to all at-risk couples.

Assessment of endometrial and subendometrial blood flow in women undergoing frozen embryo transfer cycles.

This study evaluated whether 3D power Doppler (3DPD) indices from endometrium and subendometrium can identify increases in endometrial volume/vascularity induced by exogenous oestradiol and subsequent introduction of progestogens in women undergoing frozen-thawed embryo transfer (FET). Oral oestradiol was administered at increasing doses after down-regulation to prepare the endometrium and progestogens were used for luteal support. 3DPD data sets were acquired at down-regulation, on days 5, 10 and 15 of oestradiol administration and at the time of FET. Endometrial thickness was measured using the multiplanar method and endometrial volume and blood flow from the endometrium and subendometrium were estimated using virtual organ computer-aided analysis and shell-imaging. This study evaluated 45 women at least once: 19 achieved clinical pregnancy (CP); 21 were evaluated at down-regulation (eight CP), 26 at day 5 (10 CP), 31 at day 10 (12 CP), 31 at day 15 (13 CP) and 16 at FET (seven CP). Changes were observed in all parameters between the examinations; however, differences between women who achieved CP and those who did not were not significant. 3DPD angiography is not a sufficiently sensitive tool to predict the outcome of FET. We evaluate whether 3D ultrasound using power Doppler (3DPD) indices from endometrium and subendometrium can identify predictable increases in endometrial volume and vascularity induced by serial increments in exogenous oestradiol and the subsequent introduction of progestogens in women undergoing frozen-thawed embryo transfer (FET) using hormone replacement therapy to prepare the endometrium. Oral oestradiol was administered at increasing doses after down-regulation to prepare the endometrium and progestogens were used for luteal support. 3DPD data sets of the uterus were acquired at down-regulation, on days 5, 10, and 15 of oestradiol administration, and at the time of FET. Endometrial thickness was measured. Endometrial volume and blood flow from the endometrium and subendometrium were measured using virtual organ computer-aided analysis (VOCAL) and shell imaging. This study evaluated 45 women at least once: 19 achieved clinical pregnancy (CP); 21 were evaluated at down-regulation (eight CP), 26 at day 5 (10 CP), 31 at day 10 (12 CP), 31 at day 15 (13 CP) and 16 at FET (seven CP). Changes were observed in all the parameters between the examinations; however, differences between women who achieved CP and those who did not were not significant, suggesting that quantitative 3D power Doppler angiography is not a sufficiently sensitive tool to predict the outcome of FET treatment.

Intrauterine insemination with gonadotropin stimulation or in vitro fertilization for the treatment of unexplained subfertility: a randomized controlled trial.

OBJECTIVE: To evaluate the best first line management option for the treatment of unexplained subfertility-controlled ovarian hyperstimulation (COH) with gonadotropins and IUI or IVF. DESIGN: Randomized controlled trial. SETTING: Single center trial in a tertiary referral unit. PATIENT(S): Couples with unexplained subfertility. INTERVENTION(S): Couples were randomized to receive either three cycles of IUI + COH or one cycle of IVF. MAIN OUTCOME MEASURE(S): Singleton pregnancy rate (PR) per couple. RESULT(S): A total of 207 couples were randomly assigned to three cycles of IUI + COH (n = 101) or one cycle of IVF (n = 106). There were 25 (24.7%) singleton live births for the IUI + COH group and 33 (31.1%) for the IVF group (relative risk, 1.3; 95% confidence interval [CI] 0.81-1.96) with an absolute risk difference of 6.4% (95% CI -5.8% to 18.6%). The multiple pregnancies per live birth were 4 (13.8%) for the IUI + COH group and 3 (8.3%) for the IVF group (relative risk, 0.6; 95% CI 0.14-2.4). There were no cases of ovarian hyperstimulation syndrome (OHSS) in the IUI group and three cases of OHSS (3.7%) in the IVF group. There were 17 live births from spontaneous conception in between treatment cycles (8.2%). CONCLUSION(S): The singleton live birth rate with one cycle of IVF was not significantly different than three cycles of IUI + COH. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN43430382.

An online survey of specialists' opinion on first line management options for unexplained subfertility.

The recent National Institute for Health and Care Excellence (NICE) guideline on Fertility (2012) suggests that IVF should be offered to couples with unexplained subfertility after 2 years of expectant management. The evidence on which these recommendations are based is not robust and there is a lack of agreement among specialists regarding the management of unexplained subfertility. We conducted an online survey among fertility specialists to find out the general consensus regarding the management of these couples. An e-mail questionnaire was sent to 420 reproductive medicine clinicians and 136 (32.38%) replied. Only 16% said they would always recommend IVF as the first line management for these couples, irrespective of age and duration of infertility. Of those surveyed, 39% agreed to the new NICE proposal, 33% agreed partly and 25% did not agree at all. A total of 27% of the respondents said they would definitely change their practice according to the NICE proposal but 30% said they would not; 29% said they might change their policy while the rest were unsure. This survey confirms the ongoing clinical uncertainty among fertility specialists in managing couples with unexplained subfertility.