Table 3.

Additional relevant studies that included patient education as part of a multifaceted intervention.

Author, year	Study design, location, study period, publication type	Study population	Intervention, comparator	Primary objective, secondary objective	Main results	Assessment of study
Marek et al. (2005)	Retrospective cohort study: USA. Conference abstract.	ART patients aged ≤ 37 years and patients using donor oocytes with at least two freeze-quality blastocysts. Cycle-specific analysis. n = 263 cycles (pre-intervention: 152 cycles, post-intervention: 111 cycles). Mean age and mean years of infertility were not reported.	Intervention: Multifaceted intervention. Comprehensive educational programme on twin risks. Financial incentives for SBT: free cryopreservation services and free subsequent frozen–thawed BT if needed. Comparator: Patients receiving standard care (prior to implementation of the incentive programme).	Primary objective: To evaluate use of SBT.	SBT rates for autologous cycles almost doubled (33–60%; P < 0.01) after incentive programme. SBT rates for donor cycles increased from 27% to 64% (P < 0.01). Ongoing pregnancy rates remained stable.	Strengths: Reports rates of SBT, pregnancies and multiple births before and after intervention. Distinguishes between autologous and donor cycles. Patient education included risks and complications of twin pregnancies. Weaknesses: Small sample size. No adjustment for patient characteristics. Unknown whether findings represent a single clinic or multiple centres. No information on dates of recruitment or outcomes. Not able to assess independent effect of education component. Quality of study: Level II-2 Risk for bias: High
Coetzee et al. (2007)	Retrospective cohort study: New Zealand. 2003–2004. Full-length article.	Publicly funded and private ART patients. Cycle-specific analysis. n = 280 in 2003 and n = 298 in 2004. Mean age: 36.2 years (private insurance), 33.5 years (public insurance). Mean years of infertility: not reported.	Intervention: Multifaceted intervention. Implementation of clinic-wide SET policy in 2004, written and verbal information about age-dependent twin pregnancy risks, advantages of SET, twin pregnancy risks, and free funded second cycle. Comparator: Patients receiving standard care (typically DET) in 2003.	Primary objective: To evaluate use of SET.	Rates of SET increased from 14% to 49% from 2003 to 2004. Among women aged ≤ 35 years, SET increased from 13% to 62%. The increase was greater among publicly funded patients (from 19% to 63%) than private patients (from 5% to 30%).	Strengths: Reports both rates of eSET and pregnancies by age before and after intervention, and by funding status. Weaknesses: Donor egg cycles were excluded. No adjustment for patient characteristics. Single-centre study. Not able to assess independent effect of education component. Quality of study: Level II-2 Risk for bias: High
Khalaf et al. (2008)	Retrospective cohort study: UK. July 2004– June 2007. Full-length article.	Good-prognosis ART patients (age < 40 years and extra embryos available for cryopreservation). Cycle-specific analysis, pre- and post-intervention n = 2451 [n = 1198 in 2004/2005 (pre-intervention) and n = 1253 in 2006/2007 (post-intervention)]. Mean age (female): 35.2 years (pre-intervention) and 35.8 years (post-intervention). Mean years of infertility: not reported.	Intervention: Multifaceted intervention 2006/2007. Selective SBT with an educational programme on multiple pregnancy risks and advantages of SBT. Audio-visual and written information, provided at monthly patient information seminars and during patient consultations. Information was also displayed in waiting areas. Comparator: Good-prognosis patients receiving standard care in 2004/2005 (transfer of up to three cleavage-stage embryos).	Primary objective: To evaluate CPR and MPR.	The proportion of eSET increased significantly from 1.9% (5/263) in 2004/2005 to 38% (129/342) in 2006/2007 (RR 21.9, 95% CI 9.1–52.7; P < 0.001). CPR increased from 27% pre-intervention to 32% post-intervention (P = 0.015) due to higher CPR in women with blastocyst transfer. MPR declined significantly from 32% to 17% (P < 0.001).	Strengths: Large sample size. Reports actual rather than hypothetical scenario. Weaknesses: Only 9% of cycles started in 2006/2007 had an elective SBT. Cycles involving PGD, donated oocytes or cryopreserved embryos were excluded. Patient perception of educational materials was not assessed, and effects of educational component were not assessed separately from effects of SBT strategy. Measures of association were not adjusted for confounders. Single-centre study. Not able to assess independent effect of education component. Quality of study: Level II-2 Risk for bias: High
Kodama et al. (2009)	Retrospective cohort study: Japan. December 2002–December 2003, January 2004–April 2007, May 2007–December 2008. Conference abstract.	ART patients. Cycle-specific analysis. n = 404 cycles. Mean age (female): 34.3 years (Period I), 34.4 years (Period II) and 36.5 years (Period III). Mean years of infertility: not reported.	Intervention: Multifaceted intervention. Educational counselling on twin pregnancy risks and clinic's eSBT policy. The study was divided into three time periods. Period I: 12/2002 to 12/2003 (n = 64) with a dual BT policy. Period II: 1/2004 to 4/2007 (n = 188) with eSBT for women aged < 36 years with at least two top-quality blastocysts and less than three failed BT cycles. Period III: 5/2007 to 12/2008 (n = 152) with eSBT for women aged < 40 years with at least two lower-quality blastocysts and less than three failed BT cycles and counselling about twin risks. Period III included educational counselling. Comparator: Transfers that occurred under dual BT policy with no educational counselling.	Primary objective: To evaluate MPR and PR.	The number of BTs in Period III (1.1 ± 0.03) was lower than in Periods I (1.8 ± 0.05) and II (1.5 ± 0.03) (P < 0.001). PRs were similar for these periods. MPRs in Period III (1.8%) were lower than in Periods I (28%) and II (13%) (P < 0.001).	Strengths: Compared effectiveness of eSBT and counselling on twin risks in two age groups: < 36 and < 40 years. Not able to assess independent effects of education component on MPRs. Weaknesses: No details of educational counselling provided. No adjustment for potential confounders. Single-centre study. Quality of study: Level II-2 Risk for bias: High
van Peperstraten et al. (2010)	RCT: Netherlands. November 2006–December 2008. Full-length article.	ART couples from five clinics undergoing first cycle or first cycle following successful previous ART, women aged < 40 years. n = 344. Response rate: 308/344 = 92.4%. Mean age (female): 32.0 years (intervention group), 31.7 years (control group). Mean years of infertility (couple): 2.2–2.3 years.	Intervention: Multifaceted intervention (decision aid, reimbursement offer for fourth ART cycle if SET for first two cycles with no resulting pregnancy, in person discussion of decision and reimbursement offer with nurse, followed by standard care counselling and phone call follow-up from nurse). Comparator: Standard counselling.	Primary objective: To evaluate the use of SET.	After the first treatment cycle, higher SET rate in intervention group (43%) versus control group (32%) (P = 0.05). After the second treatment cycle, higher SET rate in intervention group (26%) versus control group (16%) (P = 0.20). After the first treatment cycle, twin pregnancies were lower in the intervention group (n = 6) compared with the control group (n = 10), but this difference was not statistically significant (P = 0.33).	Strengths: RCT study encompassing five clinics. Decision aid developed from evidence-based criteria. Demonstrates cost effectiveness of SET, and cost per couple was lower in the intervention group despite free fourth cycle. Weaknesses: Limited generalizability to countries with less than three cycles of publicly funded ART cycles. Difference in SET use among two groups was lower than expected based on power calculations and sample size. Higher SET rates in intervention group could be due to reimbursement offer. Self-report bias. Greater than 20% dropout rate. Not able to assess impact of decision aid separate from multicomponent intervention Quality of study: Level I Risk for bias: Moderate
Kreuwel et al. (2013)	Retrospective cohort study: Netherlands. November 2006–December 2008 Full-length article.	Couples undergoing first ART cycle, aged < 40 years. n = 308. Response rate: 222/308 = 72.1%. Mean age (female): 31–32 years. Mean years of infertility (couple): 2 years.	Intervention: Multifaceted intervention (standard, decision aid plus free fourth ART cycle (n = 20), decision aid plus free fourth ART cycle with counselling by ART nurse (n = 37), decision aid plus free fourth ART cycle, counselling by ART nurse and follow-up phone call (n = 52). The decision aid booklet contained information about chances of and risks of singletons versus twin pregnancies. Comparator: Patients receiving standard care (n = 113).	Primary objective: To evaluate eSET rate for each intervention type. Secondary objective: To evaluate the degree to which intervention strategy influenced decision on number of embryos to transfer.	After adjustment for baseline characteristics, there was no difference in eSET rate for any of the intervention strategies, compared with standard care. Couples rated physician advice, decision aids and counselling as most important elements in decision making; reimbursement offer and phone call were ranked as least important compared with physician advice, decision aids and counselling (P < 0.001).	Strengths: Eligible couples selected from previously conducted RCT; data analysed were obtained in RCT. Able to evaluate relative importance of different types of interventions in patient decision making. Multivariate analyses used to adjust for confounders. Multi-centre study. Weaknesses: Potential bias in the selection of couples into different groups. Limited generalizability for countries that do not offer public funding of three ART cycles. No information on dates of recruitment or outcomes. Quality of study: Level II-2 Risk for bias: Moderate

ART, assisted reproductive technology; BT, blastocyst transfer; CI, confidence interval; CPR, clinical pregnancy rate; DET, double embryo transfer; eSBT, elective single blastocyst transfer; eSET, elective single embryo transfer; ICSI, intra-cytoplasmic sperm injection; mSBT, mandatory single blastocyst transfer; MPR, multiple pregnancy rate; PGD, pre-implantation genetic diagnosis; RCT, randomized controlled trial; RR, relative risk; SBT, single blastocyst transfer; SET, single embryo transfer.