Description of the condition
Worldwide, around 1.4 million women are diagnosed with breast cancer annually (GLOBOCAN 2008). In 2011, 13,110 new cases were expected to be reported in women of reproductive age in the US (ACS 2011). Adjuvant systemic breast cancer treatment may have a negative impact on fertility. Women with estrogen-receptor (ER) positive breast cancer usually undergo adjuvant hormonal treatment for five years, during which time pregnancy is contraindicated. The ovarian reserve at the age by which conception is considered to be safe for these women might be insufficient for chances of natural conception. The American Society of Clinical Oncology recommends addressing options to preserve fertility for young women early in the breast cancer trajectory (Lee 2006).
Description of the intervention
Cryopreservation of oocytes or embryos is a fertility-preserving technique that requires ovarian stimulation and should be performed before (neo)adjuvant chemotherapy is provided. Standard controlled ovarian stimulation (COS) protocols include high doses of follicle-stimulating hormone (FSH), which cause increased estrogen (estradiol) levels, and concurrent pituitary suppression by down-regulation of a woman's endogenous FSH and luteinising hormone (LH) production with gonadotropin-releasing hormone (GnRH) analogues or antagonists. COS precedes retrieval of oocytes that can be used for direct cryopreservation or in vitro fertilisation (IVF) followed by cryopreservation of embryos. Estrogen levels rise drastically during COS. For women with ER positive breast cancer, elevated estrogen levels may theoretically induce growth of tumour cells. To avoid a potentially harmful impact of COS on breast cancer outcome, women may receive an additional potentially protective endocrine agent－tamoxifen or letrozole－during COS (Oktay 2005; Oktay 2005a; Oktay 2006).
Tamoxifen is an orally administered non-steroidal anti-estrogen triphenylethylene derivative with suppressive effects on breast cancer growth (Jordan 2003). The drug is effective as adjuvant treatment in ER positive breast cancer (Clarke 2008). Letrozole is a third-generation aromatase inhibitor (AI), which systemically prevents the synthesis of estrogen from androgens by competitive, reversible binding of the enzyme aromatase CYP19. Use of third-generation AIs has long been restricted to postmenopausal women because preclinical studies have indicated that aromatase inhibition can lead to an increase in gonadotropin levels and multifollicular growth (Shetty 1997). However, with concurrent suppression of ovarian estrogen synthesis, third-generation AIs can now be used safely in premenopausal women for the purpose of providing adjuvant endocrine therapy (Goel 2009). When concurrent FSH is given to stimulate follicle growth, as in the case of COS, the co-administration of an AI attenuates estrogen levels to normal premenopausal preovulatory peak concentrations.
How the intervention might work
After oral administration of tamoxifen, metabolites are formed with high affinity for the ER that, by competitive binding, prevent estrogens from binding and activating the ER (Jordan 2007). The efficacy of tamoxifen in preventing breast cancer growth during COS is unknown. Letrozole decreases the peak estradiol (E2) level during COS (Oktay 2005; Oktay 2005a). Because the main action of AIs in the adjuvant setting is considered to come from decreasing estrogen levels to less than 50 pg/mL by blocking the aromatase enzyme that facilitates the conversion from androgens into estrogens, it is unclear how E2 levels of ˜380 pg/mL, measured during COS with letrozole, could prevent breast cancer growth. Whether the addition of tamoxifen or letrozole to standard COS diminishes the risk of subsequent breast cancer recurrence in comparison with standard COS alone in women with ER positive breast cancer remains unknown. In addition, although indications suggest that a higher number of oocytes or embryos are retrieved with the addition of letrozole to standard COS when compared with tamoxifen (Oktay 2005), the participant series are too small to allow any definitive conclusions to be drawn.
Why it is important to do this review
Young women with breast cancer have reported major fertility-related concerns before and during breast cancer treatment and have stressed the need for more information on fertility preservation (Partridge 2007; Partridge 2008). Premenopausal ER positive breast cancer patients who risk therapy-induced impairment of ovarian function rely on fertility-preserving techniques with minimal effects on breast cancer growth and unknown effects on the breast cancer－free interval. Given that most young breast cancer patients who opt for fertility preservation in current clinical practice will undergo ovarian stimulation with an approximately two-week period of iatrogenic high levels of estrogens, reproductive gynaecologists and oncologists face significant management challenges to adequately inform patients about COS.
To assess the effects of tamoxifen or letrozole, in addition to standard controlled ovarian stimulation (COS) protocols, on the breast cancer－free interval in premenopausal women with breast cancer who undergo COS for embryo or oocyte cryopreservation.
Criteria for considering studies for this review
Types of studies
Randomised trials comparing different COS protocols in women with breast cancer were eligible for inclusion.
Types of participants
Women between the ages of 18 and 42 years diagnosed with ER positive breast cancer and undergoing COS were eligible for inclusion. For women older than 42 years of age, cryopreservation of oocytes or embryos is no longer considered to be of use because of the natural fertility decline.
Types of interventions
The intervention of interest was COS with the use of FSH alone, which was considered to be the control intervention. Comparison was made with COS protocols that included the additional use of oral tamoxifen or letrozole.
Types of outcome measures
- Safety of COS, defined as recurrence-free interval (RFI) of breast cancer (the time between breast cancer diagnosis and breast cancer recurrence; locoregional recurrence, distant metastasis, or death from breast cancer, whichever occurs first) (Hudis 2007).
- COS outcome, defined as the number of oocytes or embryos retrieved and cryopreserved after COS.
- Peak estradiol levels during COS, defined as the level of estradiol on the day of human chorionic gonadotropin (hCG) injection.
- Live birth rate.
- Any adverse events.
Search methods for identification of studies
The Cochrane Menstrual Disorders and Subfertility Group (MDSG) Trials Search Co-ordinator (TSC) was consulted regarding development of the search strategy in MEDLINE, CENTRAL, EMBASE and PsycINFO. The TSC for the Cochrane Breast Cancer Group was consulted regarding searching of the Breast Cancer Specialised Register (see Appendix 1).
No language restrictions were applied to any of the searches.
We searched the following bibliographic database sources from their inception to October 2013:
- Ovid Cochrane Central Register of Controlled Trials (CENTRAL) (not limited by year of publication or language) (see Appendix 2);
- Ovid MEDLINE (not limited by year of publication or language) (see Appendix 3);
- Ovid EMBASE (not limited by year of publication or language) (see Appendix 4);
- Ovid PsycINFO (not limited by year of publication or language) (see Appendix 5); and
- EBSCOhost CINAHL (not limited by year of publication or language) (see Appendix 6).
Both indexed and free text terms were used in the search strategies.
In identifying randomised trials, the MEDLINE search was combined with the Cochrane highly sensitive search strategy, which appears in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0, Chapter 6, 6.4.11).
The EMBASE search was combined with trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) (www.sign.ac.uk/mehodology/filters.html#random).
Searching other resources
Conference proceedings from 2000 to 2012: International Federation of Fertility Societies (IFFS), American Society for Reproductive Medicine (ASRM), British Fertility Society (BFS), European Society for Human Reproduction and Embryology (ESHRE) and International Society for Fertility Preservation (ISFP) were searched. Furthermore, handsearches were performed of the proceedings of the annual meetings of the American Society of Clinical Oncology (2005 to 2010) and the San Antonio Breast Cancer Symposium (2005 to 2010).
Conference abstracts were searched on the Web of Knowledge (http://wokinfo.com/).
Trial registers were searched for ongoing and recently completed trials:
- 'ClinicalTrials.gov', a service of the US National Institutes of Health (http://clinicaltrials.gov/ct2/home); and
- World Health Organization 'International Trials Registry Platform search portal'.
OpenSIGLE database was searched for European grey literature (http://opensigle.inist.fr/).
Data collection and analysis
Selection of studies
As has been mentioned, eligibility criteria for including trials were applied by two review authors (TD and EB), who independently scanned the titles, the abstracts or both sections. All potentially relevant articles that were likely to meet the inclusion criteria were investigated in full text. No studies were found that met the inclusion criteria. When this review is updated and randomised controlled trials are available that meet our inclusion criteria, two review authors will independently investigate full text articles for compliance with the inclusion criteria and will select eligible studies according to Cochrane guidelines. Differences and disagreements will be resolved by consensus or by discussion with a third review author.
Data extraction and management
We planned that two review authors would extract all data by using forms designed in accordance with Cochrane guidelines. Any disagreements would be resolved by discussion with the senior review authors (MG, MvW and SL) and by consensus. Data would be collected from each study that met the inclusion criteria. If studies failed to provide information on time of follow-up, type of COS protocol, dosage of tamoxifen or letrozole, intention-to-treat population size, hormone receptor status, ovarian response and breast cancer outcome, original data would be sought from the principal author.
Assessment of risk of bias in included studies
We planned that all included studies would be randomised trials. The methodological quality of the included randomised trials would be assessed and reported by using the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors (TD and EB) would independently assess the risk of bias of each included study. Risk of bias assessment would comprise a description and a judgement for each entry in a ’Risk of bias’ table, where each entry would address a specific feature of the study. The methodological features to be assessed would include (1) sequence generation, (2) allocation sequence concealment, (3) blinding, (4) incomplete outcome data, (5) selective outcome reporting and (6) other potential sources of bias.
Measures of treatment effect
We planned that ordinal scales such as recurrence-free interval and peak estradiol levels during COS would be treated as continuous outcomes. Means and standard deviations (SDs) would be abstracted, calculated or requested. For continuous outcomes, mean differences (MDs) would be presented. All binary outcomes would be summarised by using the odds ratio (OR) with 95% confidence interval (CI). If data were skewed (2 × SD ± mean is greater than the highest or lowest value), we would log-transform the mean and SD within each group and then would make the comparison across groups. SDs would thus be allowed to differ in the two groups with a Taylor series approximation of the standard error (SE) (Higgins 2008).
Unit of analysis issues
We planned that all outcomes would be expressed per woman randomly assigned.
Dealing with missing data
We planned that, if we would find insufficient information in the published report of a study, we would attempt to contact the authors for clarification. If missing data became available, these would be included in the analysis. We anticipated that trials conducted over 10 years ago might not have data on live birth rates of study participants. We planned that data extracted from the trials would be analysed on an intention-to-treat basis. Where randomised cases were missing from outcome assessment, we would first contact the authors for additional data. If further data were not available, we would assume that the missing participants had failed to achieve pregnancy.
Assessment of heterogeneity
We planned that the presence of any statistical heterogeneity of treatment effect among trials would be determined using the I
Assessment of reporting biases
We planned that to evaluate external reporting bias, funnel plots for primary outcomes and for the clinical pregnancy rate would be presented, if sufficient studies were identified. If evidence of small-study effects was found, publication bias would be considered as only one of a number of possible explanations. We would also informally compare the results for live birth rates between those studies that reported live birth rates and those that did not.
If trials were sufficiently similar, Review Manager software would be used to perform meta-analyses using a fixed-effect model. Results for continuous outcomes would be combined using MD and 95% CI. For binary outcomes, the Peto approach would be applied.
Subgroup analysis and investigation of heterogeneity
We planned that if moderate heterogeneity (I
We planned that if data from more than four studies were available, sensitivity analyses would be performed. We would assess the influence of risk of bias on effect size by removing trials deemed to be at high risk. Studies with high risk of bias would include those that were not done by using an intention-to-treat (ITT) approach and those that had inadequate concealment of allocation. Analyses would be repeated by using a random-effects model to explore whether different conclusions were reached. Sensitivity analyses would be reported for the primary outcome only.
Overall quality of the body of evidence: 'Summary of findings' table
We planned that a 'Summary of findings' table would be generated by using GRADEPRO software. This table would evaluate the overall quality of the body of evidence for the main review outcomes using GRADE criteria (study limitations, that is, risk of bias; consistency of effect; imprecision; indirectness; and publication bias). Judgements about evidence quality (high, moderate or low) would be justified, documented and incorporated into the report of results for each outcome.
Description of studies
No randomised controlled trials comparing different COS protocols in women with breast cancer were found.
Results of the search
Two review authors independently screened 262 titles and abstracts that were identified by the conducted electronic searches and by screened conference proceedings, abstracts, sources of grey literature and trial registers. No randomised controlled trials were identified (Figure 1).
|Figure 1. Study flow diagram.|
No studies met our inclusion criteria.
In total, seven studies were excluded after the full text of the article had been read, because the studies did not meet our inclusion criteria. In particular, one study was excluded from the review because it was not randomised (Oktay 2005). This study compared different COS protocols in which protocols with recFSH-tamoxifen, tamoxifen alone and recFSH-letrozole were compared in 60 women with breast cancer undergoing COS for cryopreservation of embryos (Oktay 2005). A total of 29 women who underwent 33 stimulation cycles with tamoxifen alone (60 mg/d) or recFSH-tamoxifen (60 mg/d) or recFSH-letrozole (5 mg/d) were compared with a control group of 31 women with breast cancer who did not opt for fertility preservation. Compared with women who received tamoxifen alone, women who received the combination recFSH-tamoxifen or recFSH-letrozole, had a greater number of follicles. Peak E2 levels in the recFSH-letrozole group were significantly lower than in the group receiving tamoxifen alone or recFSH-tamoxifen. After 554 ± 31 days (range 153 to 1441 days) of follow-up, cancer recurrence rate was similar between women undergoing COS and women who served as a control group (three of 29 vs three of 31 women, respectively; hazard ratio, 1.5; 95% CI 0.29 to 7.4).
Risk of bias in included studies
Effects of interventions
Summary of main results
No randomised controlled trials were found that compared COS protocols with additional tamoxifen or letrozole versus standard COS protocols in women with breast cancer. Cryopreservation of oocytes or embryos is a common form of fertility preservation in women with breast cancer who risk therapy-induced ovarian failure. No evidence indicates that standard COS promotes breast cancer growth in the setting of fertility preservation before adjuvant treatment. Nevertheless, alternative COS protocols with tamoxifen or letrozole are being used on the basis of the idea that standard COS promotes breast cancer growth. Given the lack of evidence to support this idea, the use of COS protocols that include tamoxifen or letrozole should be restricted to the setting of randomised controlled trials.
Implications for practice
No available evidence supports the idea that women with breast cancer should undergo COS with the addition of tamoxifen or letrozole. Therefore, standard COS remains the first-choice regimen for women with breast cancer who wish to undergo COS for cryopreservation of oocytes or embryos.
Implications for research
Regarding the current lack of randomised controlled trials comparing standard COS protocols with alternative COS protocols, which include tamoxifen or letrozole, we stress the need for a randomised controlled trial. Tamoxifen or letrozole should be given in addition to COS only in the setting of a randomised controlled trial undertaken to compare the effects on the breast cancer－free interval of standard versus alternative COS protocols.
We want to thank Marian Showell and the editorial staff of the Cochrane Menstrual Disorders and Subfertility Group for their assistance and support, Rob Scholten of the Dutch Cochrane Center for his help during the process of title registration and Fergus Tai of the Cochrane Breast Cancer Group for his search.
Data and analyses
This review has no analyses.
Appendix 1. Cochrane Breast Cancer Group search strategy
Details of the search strategies used by the Cochrane Breast Cancer Group Specialised Register for the identification of studies and the procedure used to code references are outlined in the Group's module (www.mrw.interscience.wiley.com/cochrane/clabout/articles/BREASTCA/frame.html). We extracted trials coded with the key words ‘breast cancer’, ‘endotherapy’, ‘letrozole’, ‘aromatase inhibitor’, ‘Famara’, ‘tamoxifen citrate’, ‘tamoxifen’, ‘Nolvadex’, ‘Istubul’, ‘Valodex’, ‘embryo transfer’, ‘fertilisation in vitro’, ‘sperm injection’, ‘ovarian stimulation’, ‘vitro fertilisation’, ‘vitro fertilization’, ‘ivi-et’, ‘ivf’, ‘icsi’, ‘intracytoplasmic sperm injection’, ‘blastocyst transfer’, ‘assisted reproduction’, ‘ovulation induction’, ‘superovulation’, ‘ovarian hyperstimula’, ‘coh’, ‘cryopreservation’, ‘reproductive process’, ‘reproductive procedure’, ‘cos’, ‘fertility preservation’, ‘vitrification’, ‘cryopreservation’, ‘oocyte’, ‘embryo’, ‘ovarian induction’, and ‘ovarian hyperstimulation’ for consideration. This search was run on 6 July 2012. On October 25 the search was updated using the following terms:
CBCG SR “Tamoxifen vs Letrozole.rmd”; “Tamoxifen vs Letrozole.rmx”) (“CBCG SR Search Results (20131025).txt”); 28 records retrieved:
fertilisation in vitro
intracytoplasmic sperm injection
Appendix 2. CENTRAL search strategy
This search was run on 4 May 2012, and updated to 16 October 2013.
1 exp embryo transfer/ or exp fertilization in vitro/ or exp sperm injections, intracytoplasmic/ (1573)
2 embryo transfer$.tw. (878)
3 vitro fertili?ation.tw. (1312)
4 ivf-et.tw. (253)
5 ivf.tw. (1872)
6 icsi.tw. (647)
7 intracytoplasmic sperm injection$.tw. (405)
8 (blastocyst adj2 transfer$).tw. (64)
9 ovulation induc$.tw. (437)
10 (ovari$ adj2 stimulat$).tw. (725)
11 superovulat$.tw. (129)
12 COH.tw. (121)
13 (ovari$ adj2 induction).tw. (26)
14 exp fertility preservation/ or exp ovulation induction/ or exp superovulation/ (913)
15 COS.tw. (58)
16 fertility preserv$.tw. (6)
17 exp Cryopreservation/ (339)
18 exp Vitrification/ (2)
19 (Cryopreservation adj5 oocyte$).tw. (24)
20 (Cryopreservation adj5 embryo$).tw. (56)
21 (ovari$ adj5 hyperstimulati$).tw. (544)
22 or/1-21 (4225)
23 Tamoxifen.tw. (2539)
24 Tamoxifen/ (1266)
25 Nolvadex.tw. (72)
26 Istubal.tw. (0)
27 Valodex.tw. (0)
28 or/23-27 (2702)
29 Letrozole.tw. (348)
30 Femara.tw. (27)
31 exp Aromatase Inhibitors/ (380)
32 or/29-31 (588)
33 22 and 28 and 32 (2)
Appendix 3. MEDLINE search strategy
This search was run on 4 May 2012, and updated to 16 October 2013.
1 exp embryo transfer/ or exp fertilization in vitro/ or exp sperm injections, intracytoplasmic/ (29779)
2 embryo transfer$.tw. (7303)
3 vitro fertili?ation.tw. (15179)
4 ivf-et.tw. (1689)
5 ivf.tw. (14254)
6 icsi.tw. (4683)
7 intracytoplasmic sperm injection$.tw. (4342)
8 (blastocyst adj2 transfer$).tw. (453)
9 ovulation induc$.tw. (3131)
10 (ovari$ adj2 stimulat$).tw. (4273)
11 superovulat$.tw. (2751)
12 COH.tw. (929)
13 (ovari$ adj2 induction).tw. (205)
14 exp fertility preservation/ or exp ovulation induction/ or exp superovulation/ (9561)
15 COS.tw. (14669)
16 fertility preserv$.tw. (905)
17 exp Cryopreservation/ (25398)
18 exp Vitrification/ (193)
19 (Cryopreservation adj5 oocyte$).tw. (711)
20 (Cryopreservation adj5 embryo$).tw. (1306)
21 (ovari$ adj5 hyperstimulati$).tw. (3396)
22 or/1-21 (83916)
23 Tamoxifen.tw. (16077)
24 Tamoxifen/ (14840)
25 Nolvadex.tw. (135)
26 Istubal.tw. (0)
27 Valodex.tw. (0)
28 or/23-27 (19789)
29 Letrozole.tw. (1343)
30 Femara.tw. (76)
31 exp Aromatase Inhibitors/ (5353)
32 Aromatase Inhibitor$.tw. (4271)
33 or/29-32 (7045)
34 22 and 28 and 33 (22)
35 randomized controlled trial.pt. (326862)
36 controlled clinical trial.pt. (84071)
37 randomized.ab. (242148)
38 placebo.tw. (139649)
39 clinical trials as topic.sh. (159838)
40 randomly.ab. (177853)
41 trial.ti. (104204)
42 (crossover or cross-over or cross over).tw. (53257)
43 or/35-42 (800887)
44 (animals not (humans and animals)).sh. (3620039)
45 43 not 44 (739283)
46 34 and 45 (5)
Appendix 4. EMBASE search strategy
This search was run on 4 May 2012, and updated to 16 October 2013.
1 exp embryo transfer/ or exp fertilization in vitro/ or exp sperm injections, intracytoplasmic/ (45545)
2 embryo transfer$.tw. (9400)
3 (vitro fertilisation or vitro fertilization).tw. (18134)
4 ivf-et.tw. (2131)
5 ivf.tw. (19894)
6 icsi.tw. (7479)
7 intracytoplasmic sperm injection$.tw. (5361)
8 (blastocyst adj2 transfer$).tw. (753)
9 assisted reproduct$.tw. (10519)
10 ovulation induc$.tw. (3930)
11 (ovari$ adj2 stimulat$).tw. (5759)
12 superovulat$.tw. (2771)
13 ovarian hyperstimulation.tw. (4450)
14 COH.tw. (1174)
15 (ovari$ adj2 induction).tw. (247)
16 exp ovulation induction/ (10023)
17 exp cryopreservation/ (22707)
18 exp reproductive procedures/ (2519)
19 exp superovulation/ (1930)
20 COS.tw. (15954)
21 fertility preserv$.tw. (1491)
22 exp vitrification/ (1768)
23 (Cryopreservation adj5 oocyte$).tw. (1111)
24 (Cryopreservation adj5 embryo$).tw. (1753)
25 (ovari$ adj5 hyperstimulati$).tw. (4524)
26 or/1-25 (100619)
27 exp tamoxifen citrate/ or exp tamoxifen/ (41316)
28 Tamoxifen.tw. (20436)
29 Nolvadex.tw. (1314)
30 Istubal.tw. (5)
31 Valodex.tw. (9)
32 or/27-31 (43646)
33 exp letrozole/ or aromatase inhibitor/ (10774)
34 Letrozole.tw. (2029)
35 Femara.tw. (869)
36 aromatase inhibitor$.tw. (5767)
37 or/33-36 (12042)
38 26 and 32 and 37 (203)
39 Clinical Trial/ (864496)
40 Randomized Controlled Trial/ (320525)
41 exp randomization/ (57934)
42 Single Blind Procedure/ (15770)
43 Double Blind Procedure/ (108422)
44 Crossover Procedure/ (33662)
45 Placebo/ (197016)
46 Randomi?ed controlled trial$.tw. (73795)
47 Rct.tw. (9039)
48 random allocation.tw. (1133)
49 randomly allocated.tw. (16968)
50 allocated randomly.tw. (1796)
51 (allocated adj2 random).tw. (704)
52 Single blind$.tw. (12045)
53 Double blind$.tw. (126695)
54 ((treble or triple) adj blind$).tw. (265)
55 placebo$.tw. (173026)
56 prospective study/ (201807)
57 or/39-56 (1239726)
58 case study/ (15361)
59 case report.tw. (223356)
60 abstract report/ or letter/ (829092)
61 or/58-60 (1063318)
62 57 not 61 (1205001)
63 38 and 62 (85)
Appendix 5. PsycINFO search strategy
This search was run on 4 May 2012, and updated to 16 October 2013.
1 exp reproductive technology/ (1138)
2 in vitro fertili?ation.tw. (452)
3 ivf-et.tw. (16)
4 (ivf or et).tw. (82573)
5 icsi.tw. (37)
6 intracytoplasmic sperm injection$.tw. (32)
7 (blastocyst adj2 transfer$).tw. (2)
8 assisted reproduct$.tw. (409)
9 ovulation induc$.tw. (16)
10 (ovari$ adj2 stimulat$).tw. (44)
11 ovarian hyperstimulation.tw. (8)
12 COH.tw. (53)
13 superovulat$.tw. (5)
14 (ovari$ adj2 induction).tw. (4)
15 exp Ovulation/ (266)
16 COS.tw. (419)
17 fertility preserv$.tw. (27)
18 (Cryopreservation adj5 oocyte$).tw. (3)
19 (Cryopreservation adj5 embryo$).tw. (10)
20 (ovari$ adj5 hyperstimulati$).tw. (8)
21 or/1-20 (84459)
22 Tamoxifen.tw. (300)
23 Nolvadex.tw. (0)
24 Istubal.tw. (0)
25 Valodex.tw. (0)
26 or/22-25 (300)
27 Letrozole.tw. (30)
28 Femara.tw. (0)
29 Aromatase Inhibitor$.tw. (139)
30 or/27-29 (150)
31 21 and 26 and 30 (2)
Appendix 6. CINAHL search strategy
Last assessed as up-to-date: 16 October 2013.
Contributions of authors
Taghride Dahhan wrote the first draft of the protocol, performed the search and wrote the review.
Eva Balkenende wrote the revised draft of the protocol, performed the search and commented on the draft of the review.
Madelon van Wely contributed to the protocol with methodological and statistical expertise and commented on the drafts of the review.
Sabine Linn commented on all drafts of the protocol and review from an oncologist's point of view.
Mariëtte Goddijn, as a reproductive gynaecologist, initiated the review and supervised the development of the protocol and review.
Declarations of interest
None to declare.
Sources of support
- None, Not specified.
- None, Not specified.
Differences between protocol and review
'Randomised trial' was replaced by 'randomised controlled trial'.
We deleted the following sentences.
- 'For each reference reporting a potentially eligible trial, a copy of the full text article will be obtained'.
- 'We will also use personal communication with manufacturers, experts and specialists in the field.'
- 'Citation lists from review articles and other relevant publications will be searched.'
The definition of RFI for breast cancer was adjusted.
Medical Subject Headings (MeSH)
*Cryopreservation; *Embryo, Mammalian; *Oocytes; Breast Neoplasms [*drug therapy; metabolism]; Nitriles [*therapeutic use]; Receptors, Estrogen [metabolism]; Reproductive Techniques, Assisted; Selective Estrogen Receptor Modulators [*therapeutic use]; Tamoxifen [*therapeutic use]; Triazoles [*therapeutic use]
MeSH check words
Female; Humans; Pregnancy