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Guideline Summary
Guideline Title
Elective single embryo transfer following in vitro fertilization.
Bibliographic Source(s)
Min JK, Hughes E, Young D, Gysler M, Hemmings R, Cheung AP, Goodrow GJ, Senikas V, Wong BC, Sierra S, Carranza-Mamane B, Case A, Dwyer C, Graham J, Havelock J, Lee F, Liu K, Vause T. Elective single embryo transfer following in vitro fertilization. J Obstet Gynaecol Can. 2010 Apr;32(4):363-77. [112 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Pregnancy following in vitro fertilization

Guideline Category
Assessment of Therapeutic Effectiveness
Counseling
Management
Prevention
Risk Assessment
Treatment
Clinical Specialty
Obstetrics and Gynecology
Pediatrics
Intended Users
Managed Care Organizations
Physician Assistants
Physicians
Utilization Management
Guideline Objective(s)

To review the effect of elective single embryo transfer (eSET) compared with double embryo transfer (DET) following in vitro fertilization (IVF), and to provide guidelines on the use of eSET in order to optimize live birth rates and minimize twin pregnancies

Target Population

Women who undergo in vitro fertilization for pregnancy

Interventions and Practices Considered

Risk Assessment/Counseling/Prevention

  1. Patient informed of risks of double embryo transfer (DET) compared to elective single embryo transfer (eSET)
  2. Age of pregnant woman taken into consideration
    • Women 38 years and over
    • Women 35 years or less
    • Women 36 to 37 years
  3. Appropriate embryo transfer stage
  4. Consideration of medical or obstetrical complications
  5. Cost-effectiveness

Treatment/Management

  1. eSET vs. DET
  2. Patient and physician education
Major Outcomes Considered
  • Overall live birth rate
  • Multiple pregnancy rate
  • Cost-effectiveness
  • Quality of life

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Searches of Unpublished Data
Description of Methods Used to Collect/Select the Evidence

Published literature was retrieved through searches of PubMed, Medline, and The Cochrane Library in 2009, using appropriate controlled vocabulary (e.g., elective single embryo transfer) and key words (e.g., embryo transfer, in vitro fertilization, intracytoplasmic sperm injection, assisted reproductive technologies, blastocyst, and multiple pregnancy). Results were restricted to English language systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to November 2009. Additional references were identified through searches of bibliographies of identified articles and international medical specialty societies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Quality of Evidence Assessment*

I: Evidence obtained from at least one properly randomized controlled trial

II-1: Evidence obtained from well-designed controlled trials without randomization

II-2: Evidence obtained from well-designed cohort (prospective or retrospective) or case-control studies, preferably from more than one centre or research group

II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results from uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this category

III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

*Adapted from the Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health Care.

Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Available evidence was reviewed by the Joint Society of Obstetricians and Gynaecologists of Canada–Canadian Fertility and Andrology Society Clinical Practice Guidelines Committee and the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada, and was qualified using the evaluation of evidence criteria outlined in the report of the Canadian Task Force on Preventive Health Care.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

Not stated

Rating Scheme for the Strength of the Recommendations

Classification of Recommendations†

A. There is good evidence to recommend the clinical preventive action

B. There is fair evidence to recommend the clinical preventive action

C. The existing evidence is conflicting and does not allow to make a recommendation for or against use of the clinical preventive action; however, other factors may influence decision-making

D. There is fair evidence to recommend against the clinical preventive action

E. There is good evidence to recommend against the clinical preventive action

L. There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision-making

†Adapted from the Classification of Recommendations criteria described in the Canadian Task Force on Preventive Health Care.

Cost Analysis

Ultimately, whether elective single embryo transfer (eSET) or double embryo transfer (DET) is deemed to be more cost-effective depends on the value placed upon an additional live birth. From a societal perspective, an eSET strategy with the contribution of cryopreserved embryos appears to be more cost-effective than DET, at least in good-prognosis patients. When considering the long-term costs associated with higher morbidity in children born from multiple pregnancies, public funding of in vitro fertilization (IVF) with eSET in twin-prone patients would to be a cost-effective strategy. The cost savings could be used to fund a number of additional IVF cycles.

Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation

This clinical practice guideline has been prepared by the Joint Society of Obstetricians and Gynaecologists of Canada–Canadian Fertility and Andrology Society (CFAS) Clinical Practice Guidelines Committee, reviewed by the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the In Vitro Fertilization (IVF) Directors Special Interest Group of the CFAS, and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada and the Board of the Canadian Fertility and Andrology Society.

Recommendations

Major Recommendations

The quality of evidence (I-III) and classification of recommendations (A-E, L) are defined at the end of the "Major Recommendations."

Cumulative Live Birth Rate: The Value of Cryopreservation

Recommendations

  1. Patients should be informed of the reductions in both multiple pregnancy rate and overall live birth rate after a single fresh elective single embryo transfer (eSET) when compared with double embryo transfer (DET) in good-prognosis patients. (I-A)
  2. Because the cumulative live birth rate after fresh eSET followed by transfer of a single frozen-thawed embryo is similar but not equivalent to the rate after fresh DET in good-prognosis patients, the eSET strategy should be used in order to avoid multiple pregnancy. (I-A)
  3. Women aged 35 years or less, in their first or second in vitro fertilization (IVF) attempt, with at least two good quality embryos available for transfer should be considered good-prognosis patients. (I-A)
  4. In order to maximize cumulative live birth rates following eSET, effective cryopreservation programs should be in place. (I-A)
  5. In order to maintain the reduction in the rate of multiples achieved by fresh eSET, eSET should be performed in subsequent frozen-thawed embryo transfer cycles. (II-2A)

Blastocyst Stage Embryos

Recommendation

  1. Because blastocyst stage embryo transfer generally increases the chance of implantation and live birth compared with cleavage stage embryo transfer, eSET should be performed in good-prognosis patients who have good quality blastocysts available. (I-A)

eSET in Other Populations

Summary Statement

Indiscriminate application of eSET in populations with less than optimal prognosis for live birth will result in a significant reduction in effectiveness compared with DET. (I)

Older Women

Recommendation

  1. In women aged 36 to 37 years, eSET should be considered in good-prognosis patients with good quality embryos, particularly when blastocysts are available for transfer. (II-2A)

Summary Statement

In women aged 38 years and over, eSET may result in a significant reduction in live birth compared with DET. (II-2)

Donor Oocytes

Recommendation

  1. In oocyte donor–recipient cycles when the donor has good prognosis and when good quality embryos are available, eSET should be performed. (II-2B)

Medically or Obstetrically Indicated eSET

Recommendation

  1. In women with medical or obstetrical contraindications to twin pregnancy, eSET should be performed. (III-B)

Selective Application of eSET Results in Significant Declines in Multiples for an Entire Program

Summary Statements

  • Selective application of eSET in a small group of good-prognosis patients may be effective in reducing the overall multiple rate of an entire in vitro fertilization (IVF) population. (II-3)
  • Given the high costs of treatment, uptake of eSET would be enhanced by public funding of IVF treatment. (II-2)

Barriers to eSET

Recommendation

  1. In order to achieve successful uptake of eSET, it is essential to provide patient and physician education regarding the risks of twin pregnancy and regarding the similar cumulative live birth rate following an eSET strategy and DET. (III-C)

Economic Considerations

Recommendation

  1. When considering both direct health care and societal costs, it should be noted that live birth following eSET is significantly less expensive than DET in good-prognosis patients. (I-A) Therefore, from a cost-effectiveness perspective, eSET is indicated in good-prognosis patients. (III-A)

Definitions:

Quality of Evidence Assessment*

I: Evidence obtained from at least one properly randomized controlled trial

II-1: Evidence obtained from well-designed controlled trials without randomization

II-2: Evidence obtained from well-designed cohort (prospective or retrospective) or case–control studies, preferably from more than one centre or research group

II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results from uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this category

III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

Classification of Recommendations†

A. There is good evidence to recommend the clinical preventive action

B. There is fair evidence to recommend the clinical preventive action

C. The existing evidence is conflicting and does not allow to make a recommendation for or against use of the clinical preventive action; however, other factors may influence decision-making.

D. There is fair evidence to recommend against the clinical preventive action

E. There is good evidence to recommend against the clinical preventive action

L. There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision-making

*Adapted from the Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health Care.

†Adapted from the Classification of Recommendations criteria described in the Canadian Task Force on Preventive Health Care.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations"). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

This guideline is intended to minimize the occurrence of twin gestations while maintaining acceptable overall live birth rates following in vitro fertilization embryo transfer (IVF-ET).

Potential Harms

Not stated

Qualifying Statements

Qualifying Statements

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness
Safety

Identifying Information and Availability

Bibliographic Source(s)
Min JK, Hughes E, Young D, Gysler M, Hemmings R, Cheung AP, Goodrow GJ, Senikas V, Wong BC, Sierra S, Carranza-Mamane B, Case A, Dwyer C, Graham J, Havelock J, Lee F, Liu K, Vause T. Elective single embryo transfer following in vitro fertilization. J Obstet Gynaecol Can. 2010 Apr;32(4):363-77. [112 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2010 Apr
Guideline Developer(s)
Canadian Fertility and Andrology Society - Professional Association
Society of Obstetricians and Gynaecologists of Canada - Medical Specialty Society
Source(s) of Funding

Society of Obstetricians and Gynaecologists of Canada and Canadian Fertility and Andrology Society

Guideline Committee

Joint Society of Obstetricians and Gynaecologists of Canada—Canadian Fertility and Andrology Society Clinical Practice Guidelines Committee

Composition of Group That Authored the Guideline

Principal Authors: Jason K. Min, MD, Ottawa ON; Ed Hughes, MD, Hamilton ON; David Young, MD, Halifax NS

Joint SOGC-CFAS Clinical Practice Guidelines Committee: Matt Gysler, MD (Co-Chair), Mississauga ON; Robert Hemmings, MD (Co-Chair), Montreal QC; Anthony P. Cheung, MD, Vancouver BC; Gwendolyn J. Goodrow, MD, Cambridge ON; Ed Hughes, MD, Hamilton ON; Jason Min, MD, Ottawa ON; Vyta Senikas, MD, Ottawa ON; Benjamin Chee-Man Wong, MD, Calgary AB; David Young, MD, Halifax NS

Reproductive Endocrinology and Infertility Committee: Anthony Cheung, MD (Chair), Vancouver BC; Sony Sierra, MD (Co-Chair), Toronto ON; Belina Carranza-Mamane, MD, Sherbrooke QC; Allison Case, MD, Saskatoon SK; Cathy Dwyer, RN, Toronto ON; James Graham, MD, Calgary AB; Jon Havelock, MD, Burnaby BC; Robert Hemmings, MD, Montreal QC; Francis Lee, MD, Winnipeg MB; Kim Liu, MD, Toronto ON; Tannys Vause, MD, Ottawa ON; Benjamin Chee-Man Wong, MD, Calgary AB

Financial Disclosures/Conflicts of Interest

Disclosure statements have been received from all members of the committees.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the Society of Obstetricians and Gynaecologists of Canada Web site External Web Site Policy.

Print copies: Available from the Society of Obstetricians and Gynaecologists of Canada, La société des obstétriciens et gynécologues du Canada (SOGC) 780 promenade Echo Drive Ottawa, ON K1S 5R7 (Canada); Phone: 1-800-561-2416

Availability of Companion Documents

None available

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on October 6, 2010. The information was verified by the guideline developer on November 15, 2010.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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