Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection

Sheree L Boulet; Akanksha Mehta; Dmitry M Kissin; Lee Warner; Jennifer F Kawwass; Denise J Jamieson

doi:10.1001/jama.2014.17985

Assisted Reproduction · Outcomes and Effectiveness

Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection

Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ

Published January 20, 2015 JAMA

DOI 10.1001/jama.2014.17985 PMID 25602996 PMC PMC4343214

RRM Academy Synopsis

ICSI use in US IVF doubled with no better postfertilization outcomes

In 1,395,634 fresh US IVF cycles, use of intracytoplasmic sperm injection (ICSI) rose from 36.4% in 1996 to 76.2% in 2012. ICSI was not associated with improved postfertilization outcomes, with or without male factor infertility.

Key Findings

Across 1,395,634 fresh IVF cycles from 1996 through 2012, ICSI was used in 908,767 cycles (65.1%). Male factor infertility was reported in 499,135 cycles (35.8%).
With male factor infertility, ICSI use climbed from 76.3% (10,876/14,259) to 93.3% (32,191/34,506). Without it, use climbed from 15.4% (4197/27,191) to 66.9% (42,321/63,250). Both trends had P < .001.
In male factor cycles from 2008-2012, cancellation after retrieval was 6.3% with ICSI vs 13.6% with conventional IVF (adjusted RR, 0.50; 95% CI, 0.45-0.56).
After adjustment, those male factor cycles had comparable pregnancy, miscarriage, and live birth rates. Their multiple birth rate was lower with ICSI (30.9% vs 34.2%; adjusted RR, 0.87; 95% CI, 0.83-0.91).
Without male factor infertility (317,996 cycles), ICSI was associated with lower implantation (23.0% vs 25.2%) and live birth (36.5% vs 39.2%); adjusted RRs 0.93 and 0.95, 95% CIs 0.91-0.95 and 0.93-0.97.

Interpretation

The study is a retrospective cohort, which analyzes records already collected. The records come from a national surveillance system that does not link repeat cycles for one patient. The system holds no fertilization rates and no direct measure of embryo quality. The authors note possible bias from uncontrolled confounding. Differences in cycles without male factor infertility were small, and the authors say a large sample may explain them. Only fresh cycles in the United States were analyzed.

RRM Context

The authors say ICSI bypasses natural barriers to fertilization. Two practice committees found too little evidence for its routine use without male factor infertility. That diagnosis appeared in 35.8% of these cycles. Restorative reproductive medicine seeks the cause in both partners. A procedure that bypasses the natural barriers to fertilization leaves that question open.

Our editorial summary of this paper, not the article's abstract.

Abstract

Importance

Intracytoplasmic sperm injection (ICSI) is increasingly used in patients without severe male factor infertility without clear evidence of a benefit over conventional in vitro fertilization (IVF).

Objective

To assess national trends and reproductive outcomes for fresh IVF cycles (embryos transferred without being frozen) following the use of ICSI compared with conventional IVF with respect to clinical indications for ICSI use.

DESIGN, SETTING, AND

Population

Retrospective cohort study using data on fresh IVF and ICSI cycles reported to the US National Assisted Reproductive Technology Surveillance System during 1996-2012.

Main Outcomes and Measures

Trends in ICSI use during 1996-2012 with respect to male factor infertility, unexplained infertility, maternal age 38 years or older, low oocyte yield, and 2 or more prior assisted reproductive technology cycles; reproductive outcomes for conventional IVF and ICSI cycles during 2008-2012, stratified by the presence or absence of male factor infertility.

Results

Of the 1,395,634 fresh IVF cycles from 1996 through 2012, 908,767 (65.1%) used ICSI and 499,135 (35.8%) reported male factor infertility. Among cycles with male factor infertility, ICSI use increased from 76.3% (10,876/14,259) to 93.3% (32,191/34,506) (P < .001) during 1996-2012; for those without male factor infertility, ICSI use increased from 15.4% (4197/27,191) to 66.9% (42,321/63,250) (P < .001). During 2008-2012, male factor infertility was reported for 35.7% (176,911/494,907) of fresh cycles. Among those cycles, ICSI use was associated with a lower multiple birth rate compared with conventional IVF (30.9% vs 34.2%; adjusted relative risk [RR], 0.87; 95% CI, 0.83-0.91). Among cycles without male factor infertility (n = 317,996), ICSI use was associated with lower rates of implantation (23.0% vs 25.2%; adjusted RR, 0.93; 95% CI, 0.91-0.95), live birth (36.5% vs 39.2%; adjusted RR, 0.95; 95% CI, 0.93-0.97), and multiple live birth (30.1% vs 31.0%; adjusted RR, 0.93; 95% CI, 0.91-0.95) vs conventional IVF.

Conclusions and Relevance

Among fresh IVF cycles in the United States, ICSI use increased from 36.4% in 1996 to 76.2% in 2012, with the largest relative increase among cycles without male factor infertility. Compared with conventional IVF, ICSI use was not associated with improved postfertilization reproductive outcomes, irrespective of male factor infertility diagnosis.

Topics

Assisted Reproduction › Outcomes and Effectiveness › Outcomes by Diagnosis · Male Fertility › Male Factor Treatment › Medical Management

Sheree L Boulet, Akanksha Mehta, Dmitry M Kissin, Lee Warner, Jennifer F Kawwass, Denise J Jamieson

S Boulet, A Mehta, D Kissin, L Warner, Jen Kawwass, Jenny Kawwass, J Kawwass, D Jamieson

PMID 25602996 25602996 DOI 10.1001/jama.2014.17985 10.1001/jama.2014.17985 Boulet et al. 2015, Boulet 2015

Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection

ICSI use in US IVF doubled with no better postfertilization outcomes

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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