The fate of surplus embryos in the setting of assisted reproductive technology: A scoping review

I Gusti Agung Ngurah Agung Sentosa ,Sarrah Ayuandari ,Rafhani Rosyidah ,Agung Dewanto?

1Department of Obstetrics and Gynaecology Division of Reproductive Endocrinology Fertility,Faculty of Medicine,Public Health and Nursing,Gadjah Mada University,Yogyakarta,Indonesia

2Departement Midwifery,Muhammadiyah University,Sidoarjo,East Java,Indonesia

ABSTRACT Objective: To identify the attitudes of infertile couples toward their surplus frozen embryos.Methods: This study was according to PRISMA-ScR as the guideline for scoping review.Studies that assessed the attitudes of patients or infertile couples who had surplus embryos were included.We conducted systematic searches in English studies from April 2011-April 2021 using 7 databases: PubMed,Science Direct,EBSCO,Scopus,the Cochrane Library,Sage Journals,and Google Scholar.Data were charted based on author,year of publication,country,purpose,data collection,key findings,and research focus/domain.Results: A total of 37 research articles were included in the analysis.Their attitudes encompassed: supporting the donation of the surplus embryos for both research and reproductive purposes,continuing to store the frozen embryos,and disposing of the surplus embryos.Conclusions: Most of the infertile patients support donating their surplus embryos for research and reproductive purposes.

KEYWORDS: Attitude;Decision making;Infertile patients or couples;Male infertility;Female infertility;Surplus embryos;Embryo disposition;Embryo leftover

1.Introduction

Rapid developments in the field of assisted reproductive technology,and a consequent greater success rate in achieving pregnancy at the first cycle ofin vitrofertilization (IVF) programs,have led to a surplus of embryos.The number of surplus embryos that could be stored is limited by the storage capacity.This limitation certainly affects the number of embryos that could be kept by an infertility clinic that performs assisted reproductive technology procedures.In addition,a woman's ability to conceive embryos and become pregnant was also a limitation. Surplus embryos are the excess of frozen embryos achieved by a woman after she is successfully treated in the IVF program and she also had the desired number of children as a result of the program.The excess of frozen embryos has been increasing in numbers due to the increasing number of oocytes obtained during ovum pick-up and the increase in the cumulative rate of live births[1].A previous study found that there were various attitudes towards the excess of frozen embryos,including continuing to or ceasing to store the frozen embryos[1,2].In the 1990s,patients generally preferred to dispose of the excess embryos,but since the early 2000s,this attitude has been reversed[2].Another proposed option against the need for further storage by the clinician was a transfer method,which included thawing and transfer of a surplus embryo into the patient's vagina/cervix or the uterus during infertile periods in the patient's menstrual cycle without hormonal therapy[3].Various factors could influence the attitude of infertile couples who have surplus embryos,including environmental conditions,parental experiences,information obtained,personal value,and psychosocial or demographic factors[4].In addition,the conceptualization of embryos,trust in medical science,and the lack of acceptable options are also the contributing factors that influence infertile couples' attitudes toward their surplus embryos[5].However,attitudes will vary among couples.Therefore,this study aimed to analyze the attitude of patients or infertile couples toward excess/surplus embryos.

2.Materials and methods

2.1.Protocol

This scoping review was conducted based on a framework developed by Joanna Briggs Institute and following the PRISMAScR checklist[6].This scoping review was described to identify the attitude of infertile couples toward their surplus frozen embryo.

2.2.Eligibility criteria

The inclusion criteria in this scoping review were research articles with clinical trial design,library reviews,case studies/series,and other descriptive studies that discussed the choice of patient/infertile partner attitudes towards surplus embryos.

The exclusion criteria in this scoping review were source data in the form of commentaries,such as letters to editors,the manuscript which did not have full text,and the article that was not in English.

2.3.Information source

A three-step search strategy was utilized based on Joanna Briggs Institute’s recommendations.A systematic literature search was conducted to identify studies/articles reporting on the attitudes of infertile patients or couples who have surplus embryos.A search was conducted on seven databases including PubMed,ScienceDirect,EBSCO,Scopus,the Cochrane Library,Sage Journals,and Google Scholar from April 2011 to April 2021.

2.4.Searching evidence

The search string used was as follow: Medical Subject Heading (MeSH) namely (((((((((″Attitude″[Mesh]) OR ″Attitude to Health″[Mesh]) OR ″Decision Making″[Mesh]) OR ″Decision Making,Shared″[Mesh]) OR ″Decision Theory″[Mesh]) OR ″Reproductive Behavior″[Mesh]) OR ″Directive Counselling″[Mesh]) OR ″Patient Self-Determination Act″[Mesh]) OR ″Patient Participation″[Mesh]) OR ″Involuntary Fertility Control″[Mesh] AND (((″Infertility″[Mesh]) OR ″Infertility,Male″[Mesh]) OR ″Infertility,Female″[Mesh]) OR ″Fertility Clinics″[Mesh] AND (((((“Surplus Embryo”[Mesh]) OR ″Research Embryo Creation″[Mesh]) OR ″Embryo Research″[Mesh]) OR ″Embryo Disposition″[Mesh]) OR ″Cryopreservation″[Mesh]) OR ″Fertilizationin Vitro″[Mesh]) OR “Embryo Leftover”[Mesh]).

2.5.Selection of source of evidence

By working independently and avoiding duplication,two authors (IG and SA) decided upon which titles and abstracts to include.Duplication was avoided by using the software Mendeley Desktop version 1.19.8.Abstracts that had the potential to meet the criteria but with a lack of information were further studied using the full document if they did not meet the criteria were excluded.

2.6.Data charting process

All data from articles included in the scoping review were extracted.Extracted data included author,year of publication,country,purpose,data collection,key findings,and research focus/domain.

2.7.Data item

These extracted data were listed in the table by using Microsoft Excel 2010 and were classified based on author,year of publication,country,purpose,data collection,key findings,and research focus/domain.

2.8.Summarizing evidence

The extracted data were summarized and classified based on the country of origin of the articles,study design of articles,methods to conduct the articles,and options against the storage of surplus embryos.

3.Results

3.1.Selection of source and characteristic of evidence

From the seven database sources,4 196 studies were obtained,and after the separation of duplication,it was reduced to 2 729 research articles.From this,246 papers met the eligibility criteria,and 37 papers met the inclusion criteria.Figure 1 shows the results of this systematic search process.Characteristics of studies that meet inclusion criteria are available in Table 1.The countries of origin,the study design and the methods of the included studies are mentioned in Table 2.

Figure 1.PRISMA-ScR flowchart in article and result search.

3.2.Attitudes options toward surplus embryos

Several options can be extracted from the studies regarding the attitudes toward the surplus embryos,which are described in Table 3.

Table 1.Data extraction from individual studies.

Table 1.Data extraction from individual studies (continued).

Table 1.Data extraction from individual studies (continued).

Table 2.Country of origin,study design and methods of the included studies.

Table 3.Option,reason,factor,and barrier that influence decision/attitude.

3.2.1. Embryo donation

There were 31 studies discussing donation options from surplus frozen embryos.These studies came from Canada,the United States of America (the USA),Mexico,Italy,Israel,Portugal,France,Sweden,Belgium,China,Japan,India,Iran,and Australia.The donation option was divided into two types that are: donations for the reproductive purposes of other infertile couples and donations for research purposes.Based on the continent of origin of the studies,most of the subjects who chose to donate surplus embryos were from Europe followed by Asia,America,and Australia.Countries from Latin America such as Brazil,Venezuela,Colombia,Peru,Bolivia,Uruguay,and Ecuador also tended to donate surplus embryos for research purposes[7].Study showed that in Italy (n=832) donation options for research were also very high which was approximately 84% of the surplus of aneuploidy embryos[11].The Zoroastrians in Iran (n=143) also donated surplus embryos for reproduction purposes (71.3%)[24].

In Portugal (n=221),87.3% of the subject under the age of 36 chose to donate embryos[22].Studies showed that in the USA (n=224),the percentage going to the two choices of donations,in general had not reached 50%,whereas in 2019 research showed the choice of donations for research was only 29% and donations for reproduction by 13%[10].Even a subsequent study in 2020 showed that the choice of donation for research only reached 45.4%[2].The results of the study in Belgium (n=326) showed that the percentage of donation options for research purposes was 50.8% and the percentage of donations for reproduction was 16.1% from the group of 61.3% of couples who did not continue to store the surplus embryos[33].Donation for research in Belgium (n=2 334) has been increasing year by year compared to donations for reproduction[32].Overall,the percentage of subjects who donated surplus embryos in Japan (n=2 605) was 36.2% while in China (n=718) and Canada (n=498),embryo donation options for research were 16.4% and 56.0%[15,16,25].When viewed by gender,infertile in Japan (n=2 605) tended to donate embryos[15].In China (n=718),women over the age of 30 preferred to donate their embryos.Donation options for research and reproduction in India were 11.5% and 46.0% respectively (n=87) with the percentages of male and female patients choosing embryo donation being 23.7% and 15.7%,respectively (n=594)[12,13].The donation option for research in Israel (n=674) was only 7%[8].Research in Sweden (n=471) showed that the percentages for the two embryo donation options were 73%,with 55% for research and 45% for reproduction[29,30].

3.2.2.Continuing to keep frozen embryos

There were eleven studies discussing the continuation of surplus embryo storage.These studies came from Canada,the USA,Israel,Belgium,China,and Japan.The option to continue the storage of surplus embryos had increased in Israel (n=674)[8].Research in the United States (n=1 053) also showed the option to continue the storage of frozen embryos was 79%[10],meanwhile,in China (n=769) it was 64.3%[16].Qualitative research in Canada (n=45) showed that the option to continue the storage of frozen surplus embryos was 50% of the sample group[19].Between 30% and 50% of the patients who participated in the study in Belgium (n=231) and the Netherlands (n=95) expressed a desire to keep keeping frozen embryos[34,36].

3.2.3.Embryo disposition

There were ten studies discussing embryo disposition.These studies come from Canada,the USA,Belgium,China,Japan,and Australia.In a study conducted in the United States (n=615),the choice to dispose of the embryos was 50.5%,which was higher in female patients who were less than 30 years old[2].Meanwhile,in Canada (n=131),the study showed that the percentage of the population that would dispose of surplus embryos was 37%[18].In Belgium (n=200),87.9% opted not to continue surplus embryo storage with 27.1% deciding to dispose of the embryos.Other studies in the United States (n=400) showed that embryos obtained from egg donors compared to autologous eggs tended to be discarded (38%).The option to discard embryos was preferred by Asians living in the United States[35,39].In China (n=363),the study showed that 58.8% of couples chose to dispose of surplus embryos[27].

4.Discussion

These studies determine the attitude of patients or infertile couples toward excess/surplus embryos.The focus of this study is the choice made for embryo disposition that is,to store,donate or discard embryos.There was also another choice mentioned in the paper which is to re-insert the embryo into the uterus,however,it did not become a focus area in this scoping review.Studies from different countries show that most infertile couples choose to donate their surplus embryos.Some of the factors that influence this decision include a belief that it will assist in the development of science: a positive view of research,a great sense of trust in the health system,and a desire to help other infertile couples[23,40].Further analysis shows the donation of surplus embryos for research was generally made if the couple viewed the embryo as a research sample.However,if the couples viewed the embryo as a potential human being,then it became a factor in choosing to donate for reproduction[4].One study indicates the attitudes of those who donate embryos for reproduction can be characterized as being pragmatic and optimistic with a greater consciousness of the importance of social bonds[28].Another study identifies the factors influencing an embryo donation program for reproduction as follows: the perception of the embryo,unwillingness to dispose of embryos or commit to its storage;a sense of responsibility as a parent for the embryos;and the desire to engage with embryo recipients[38].

Couples who chose to continue with the storage of surplus embryos felt a sense of morality towards the embryos and the desire to save them for subsequent reproductive efforts[10,16,27].Meanwhile,couples who wanted to dispose of embryos felt that there was: a lack of information/explanation received;a negative perception toward research;high cost of storage,and;now having the desired number of children[22,27].One study indicates a five-stage decision-making model for frozen embryos comprising 1) a moratorium on transfer;2) the storage embryo and having additional children are considered;3) the cost of storage is considered;4) the partner’s opinion is confirmed on continued storage,and;5) the effect of donation[5].Differences in the attitudes to choices by infertile couples from each country are likely influenced by local cultural factors,applicable rules,ethical views,and information received.In China,embryo donation is preferred most likely due to sociocultural public perceptions[14].In Australia,the regulations and practices regarding embryo donation are still lacking[28].Whereas,in Belgium,there is a perception that embryos are a symbol of a relationship with a partner,which causes difficulties in making choices to dispose of surplus embryos with consequent guilty feelings and regrets[31].Emotional conflicts in the decision-making for surplus embryos occur in 39% of couples in the USA[37].There were nine studies that had participation rates below than 90%[11,18,29-31,33,34,36,37] and most of them used descriptive-analytical study method[18,29-31,33,34,36,37].The results of this review can provide case studies,knowledge,and consideration for fertility experts on establishing a policy toward surplus embryos in their clinical setting.

There were limitations and weaknesses in most of the reviewed studies,such as the participation rate of the sample was still very low and had not reached greater than ＞90% of the total samples.This certainly affected the aggregate picture of these study results because not all subjects provided information regarding attitudes to choices for surplus embryos disposition.Most studies with descriptiveanalytical methods also might influence the analysis of the result,because decisions and attitudes were longitudinal and might change over time during the storage of the embryos.

In conclusion,most infertile couples chose to donate surplus embryos for research and reproduction.In the future,more multinational cohort research with a subject participation rate above ＞90% is needed to be able to better understand the aggregated picture of couples’ attitudes toward surplus embryos.

Conflict of interest statement

The authors declare there is no conflict of interest.

Funding

The study received no extramural funding.

Authors’ contributions

Agung Dewanto provided the definition,concept,and design of intellectual material.Investigation,literature search,and data analysis were all done by I Gusti Agung Ngurah Agung Sentosa and Sarrah Ayuandari.I Gusti Agung Ngurah Agung Sentosa,Sarrah Ayuandari,Rafhani Rosyidah,and Agung Dewanto wrote,edited,and reviewed the paper.