A scoping review of infertility research conducted in the Republic Of Ireland

Search strategy

The search strategy had four components. First, electronic searches were conducted across five electronic databases in March 2023: Medline, CINAHL, Academic Search Complete, PsycInfo, and Psychology and Behavioural Sciences Collection. The development of the search strategy was supported by a Research Librarian. The search strategy (for Medline search strategy, see Table 1) consisted of subject headings along with free-text keywords and was adapted as necessary for use across the different databases. Second, the reference lists of all studies identified as eligible for inclusion were screened to identify additional eligible articles. Third, searches were undertaken across ProQuest, Google (first 100 returns for each search, location set to Ireland), and Google Scholar (first 100 returns for each search, location set to Ireland) to identify relevant grey literature. Finally, in recognition of the inclusion of Irish data on ART success rates in international reports, the list of publications from the European Society of Human Reproduction and Embryology (ESHRE) and the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) were screened.

Study selection

Inclusion and exclusion criteria. In order to be included, studies were required to have a primary focus on infertility or infertility care, to be written in English, and to have been conducted in RoI. Eligible studies could include persons experiencing infertility or healthcare professionals or institutions that provide treatment to persons experiencing infertility.

Studies were excluded if they: a) were solely laboratory-based with no clinical data (e.g., pregnancy rates) presented; b) related to pregnancy loss without a focus on persons experiencing infertility; c) related to contraception or family planning, pregnancy, and termination of pregnancy; d) were solely concerned with the genetic components of infertility; e) were conducted in countries other than RoI, did not explicitly state where data was collected, or presented data from RoI alongside data from other countries and it was not possible to extract RoI-specific data; e) did not report original research or were only available as a conference abstract; f) consisted of a case report or a series of these, or; g) focused on fertility preservation for cancer patients.

Screening. Titles and abstracts of records returned during the electronic searches were exported to Endnote© (https://endnote.com/; Zotero (https://www.zotero.org/) may be considered as a free alternative that can perform equivalent functions) for removal of duplicates and recordkeeping. The screening of all records was conducted in duplicate using Microsoft Excel© (https://www.microsoft.com/en-ie/microsoft-365/excel; Google Sheets (https://www.google.com/sheets/about/ may be considered as a free alternative that can perform equivalent functions). Where eligibility was unclear, full-texts were reviewed. For papers where inclusion was unclear, or in instances where two reviewers differed, the wider research team was consulted. A careful record was maintained to document the review of full-texts and primary reasons for exclusion, as relevant.

Data extraction. For each study, data were extracted by two independent reviewers on study aim, design (categorised as either quantitative, qualitative, mixed or multiple methods), methodology, participants, setting, measures, and key findings into a data extraction tool presented within Microsoft Word© (https://www.microsoft.com/en-ie/microsoft-365/word; Google Docs (https://www.google.com/docs/about/) may be considered as a free alternative that can perform equivalent functions). The data extraction tool was developed as per Pollock et al.¹⁹’s guidance on best practice for data extraction, analysis, and presentation within scoping reviews. The tool was piloted across five studies. Any disagreements in data extraction were resolved through discussion.

Data synthesis. Narrative synthesis, as described by Popay et al.²⁰, was undertaken to collate the extracted data. Deductive content analysis²¹ was also used to cluster studies by area of research. Specifically, the researchers worked together to consider the data extracted for each study and to categorise its research area. An initial list of infertility-related research areas was developed using the research priorities reported within Garcia et al.²² and Duffy et al.²³. These initial codes were refined, and added to, by the researchers to reflect the diversity and foci of included studies. Ultimately, thirteen distinct research areas (see Table 2) were used to cluster studies.

Safety of treatments

Two studies (1.9%) considered the safety of ART-related treatments. One study²⁴ identified oestradiol levels (15,000 pmol/L) and number of oocytes (≥20) that were predictive of hospital admissions for ovarian hyperstimulation syndrome. The other assessed the effects of a mixture of fentanyl and midazolam as analgesia during oocyte retrieval.

Psychosocial wellbeing during infertility

Seven studies (6.7%) examined psychosocial wellbeing during infertility. For instance, one study²⁵ explored whether psychological stressors were related to ART outcomes and found no differences in wellbeing, support, or stress among those who conceived versus those who did not. Walsh et al.²⁶ explored anxiety and readiness around potential twin pregnancies. Three of the studies^27–29 engaged exclusively with men experiencing infertility, examining how it impacted their psychological wellbeing and exploring factors predictive of distress. One study²⁸ revealed a negative impact of male factor infertility on sense of masculinity and body impact, feelings of stigmatisation and social isolation, and the importance of a supportive relationship for wellbeing. Another²⁷ revealed significant negative associations between infertility distress and self-esteem, mental health, and relationship satisfaction. The third study²⁹ identified no symptoms of depression among participating men but found that over 30% presented with anxiety.

Healthy habits

Two studies (1.9%) were concerned with exploring healthy habits among women experiencing infertility. One study³⁰ examined levels of compliance with cervical screening, status of rubella immunity, and folic acid supplementation in women beginning In-Vitro Fertilisation (IVF). Overall, poor levels of compliance were observed. The other study³¹ was focused on folic acid specifically and found that although 64% of participating women were aware of recommendations, only 58% understood these and only 26% were compliant.

Success rates of ART

Thirty-three studies (31.4%) were concerned with ART success rates. These studies were typically outputs from ICMART or ESHRE. The Irish success rates reported varied from year to year. Delivery rates for IVF were as low as 18.6%³² and as high as 39.5%³³ per transfer. For Intracytoplasmic Sperm Injection (ICSI), delivery rates were as low as 18.8%³² and as high as 38.3%³⁴ per transfer. For frozen embryo transfers (FETs), delivery rates were as low as 7.9%³⁵ and as high as 30.5%³³. The number of Irish clinics returning data varied from as low as 1 clinic up to 6 clinics year-on-year. Not all papers categorised as focusing on success rates were outputs from ICMART or ESHRE. For example, Geisler and colleagues³⁶ reported on the outcomes, and predictors of these, from 851 couples undergoing Intrauterine Insemination (IUI). They reported lower age and multiparity as predictors of success, and a cumulative pregnancy rate of 34.9% over three IUI cycles.

Risks associated with ART

Four studies (3.8%) focused on the risks associated with ART. Two^37,38 assessed for differences in the outcomes of twin pregnancies conceived via ART and those spontaneously conceived, and found no significant differences. Another study³⁹ compared IVF and spontaneous pregnancies and identified higher rates of miscarriage and pregnancy complications among the IVF group. The final study⁴⁰ examined birth weight and multiple births among ART pregnancies as compared to spontaneous pregnancies and found that multiple births and low birth weight were more common⁴¹ for ART pregnancies, particularly in the case of multiple births.

Alternative and supplemental treatments

Five (4.8%) studies considered the use of alternative and supplemental treatments to ART. Two studies⁴² evaluated restorative reproductive medicine for couples experiencing infertility, with one reporting a live birth rate of 18.4% across 403 couples within 24 months of treatment and the other reporting a live birth rate of 25.5% within 24 months. Other studies explored the impact of other procedures including myomectomy⁴³ and the use of bromocriptine in hyperprolactinaemic women⁴⁴. The final study⁴⁵ examined the prevalence of herbal medication usage among women availing of ART.

Gamete quality and ovarian reserve

Three studies (2.9%) considered gamete quality or ovarian reserve. One study⁴⁶ compared semen samples during treatment to those collected during initial testing and found a significant increase in sperm motility on the day of oocyte recovery. Two studies^47,48 explored anti-müllerian hormone (AMH) levels in infertile populations offering a mean AMH level (17.86 pmol/L⁴⁷ and 18.87 pmol/L⁴⁸) and reporting a decrease in mean AMH of 1.72 pmol/L per year⁴⁷.

Causes of infertility

Two studies (1.9%) focused on causes of infertility. O’Driscoll et al.⁴⁹ explored the causes of infertility for 50 Irish couples in the 1950s and identified male factor infertility as the cause in 20% of cases, tubal factors in 38% of cases, ovarian causes in 16% of cases and psychological and miscellaneous factors in 12% of cases. Skrabanek and colleagues⁵⁰ assessed the frequency with which hyperprolactinaemia was identified among patients being investigated for reproductive and endocrine disorders.

Service description and evaluation

Thirteen studies (12.4%) focused on service description and evaluation. They typically described the initiation of a new service and outcomes or experiences during the early months. Examples included a joint gynaecology and urology clinic established at St James’s Hospital⁵¹ and a fully outpatient-based, self-financing, IVF service established in the Rotunda Hospital⁵². Other papers described the early use of particular infertility treatments in Ireland such as ICSI⁵³, testicular sperm extraction⁵⁴, or dual anonymous gamete donation⁵⁵.

Ethics, access, and organisation of care

Nine studies (8.6%) considered a variety of issues pertaining to ethics, access, and organisation of infertility care. Three studies^56–58 considered ART legislation in Ireland, with one⁵⁷ examining how its absence impacts patients’ experiences and another⁵⁸ engaging healthcare providers regarding draft legislation. One study⁵⁹ considered cost of, and access to, ART, reporting an average cost of 5,400e per ART cycle in Ireland. Another study⁶⁰ considered additional hidden costs of IVF, reporting that these increased with additional distance from the fertility clinic with accommodation costs particularly significant. Two studies⁶¹ considered the impact of COVID on ART provision, with one⁶¹ exploring patients’ reactions to risk mitigation strategies and pregnancy advice and the other⁶² profiling the impact on services nationally as compared to other countries. One study⁶³ engaged fertility patients regarding their attitudes to, and opinions around, donor activity within ART. The last study⁶⁴ examined the characteristics of patients who “abandoned” frozen embryos.

Quality of service provision

Three studies (2.9%) focused on the quality of service provision experienced by fertility patients. One study⁶⁵ explored the source and transmission of microorganisms during IVF and found 50% of cycles had microorganisms grown in any fluid culture but patient outcomes were independent of microbial presence. Another⁶⁶ examined patient satisfaction with pharmacy services provided during ART. It identified an overall pharmacy complaint rate of 11.8%, with problems being reported more frequently in relation to community pharmacies rather than specialty pharmacies. The final study⁶⁷ explored how the clinic setting contributes to patients’ experiences, and involved the assessment of two fertility clinics across variables such as privacy available and friendliness of staff.

Optimising treatment regimes or protocols

Twelve studies (11.4%) examined potential means of optimising ART treatment regimes or protocols. These studies explored various changes to treatment protocols such as varied exogenous luteinizing hormone (LH) dosages⁶⁸, fresh versus frozen embryo transfer⁶⁹, the use of culture medium versus saline solution for follicular flushing during oocyte retrieval⁷⁰, the duration of gonadotropin stimulation⁷¹, and single versus double embryo transfer⁷². The impact of these modifications varied; for instance, higher LH dosages were significantly associated with implantation rates but not with live birth rates⁶⁸; cumulative pregnancy rate was similar with both single and double embryo transfer⁷² and for fresh and frozen embryo transfers⁶⁹; there was no impact of duration of gonadotropin stimulation on clinical pregnancy rates in IVF⁷¹, and; pregnancy rates were similar whether culture medium or saline solution were used for follicular flushing⁷⁰. Other studies looked at treatment protocols beyond IVF. For instance, Oduola et al.⁷³ compared the outcomes of ovulation induction via timed sexual intercourse (TSI) or IUI for ovulatory women versus anovulatory women and different ovulation induction regimens.

Exploring factors that may predict treatment outcomes

Ten studies (9.5%) explored factors that might predict ART outcomes. Factors assessed included lifestyle and demographic factors (e.g., alcohol intake)⁷⁴, physical factors (e.g., uterine dimension)⁷⁴, biochemical factors (e.g., ovarian reserve)⁷⁴, uterine natural killer cells⁷⁵, vitamin D status⁷⁶, age^77,78, serum oestradiol per oocyte ratio⁷⁹, previous IVF failures, and metabolomics analysis of follicular fluid⁸⁰. Factors that were identified as being predictive of treatment outcomes were markers of ovarian reserve⁷⁴, uterine natural killer cell populations⁷⁵, age^77,78, characteristics of follicular fluid⁸⁰, and serum oestradiol per oocyte ratio⁷⁹. One study⁸¹ explored predictors of spontaneous conception in patients with a prior successful ART pregnancy and identified younger age, shorter infertility duration, unexplained infertility, and endometriosis as predictors.

Limitations

There are a number of limitations to our review which should be noted. First, there was a small number (n=8) of potentially relevant articles for which we were unable to access full-texts. We must therefore acknowledge the possibility that some relevant articles that should have been included were not. Second, we did not assess the quality of the included studies. This is typical for scoping reviews⁹⁰, and is a recognised limitation. Third, no stakeholder engagement was undertaken as part of the current review. A stakeholder consultation phase is considered optional within scoping reviews⁹¹ but may contribute to contextualising the data and determining the recommendations to result from the review. We have suggested a national priority setting exercise, and the data from the current review might usefully guide stakeholders within this process.

Suggestions for future international comparative research

Our review has offered a clear overview of the current infertility research landscape in RoI, the identification of research gaps, and clarity regarding how research has addressed recognised infertility research priorities. It may therefore be recommended that similar reviews consider research outputs on infertility in other countries, or more widely across Europe in order to identify intra-country differences and commonalities. We can find no similar national reviews of infertility research. There continues to be substantial variability in availability of ART services across Europe and in ART pregnancy and delivery rates¹⁵. Such data convey the necessity of understanding and advancing research within individual countries, contexts, and health systems as well as internationally. Scoping reviews can offer significant value for stimulating research in individual countries and might facilitate important country-to-country comparisons.

Suggestions for future Irish research

As RoI begins to introduce state-funded ART⁹, it will be important that researchers prepare to evaluate the implementation of these services, including consideration of patient and provider experience and clinical outcomes. Further, RoI continues to lack ART legislation and a national registry of ART activity. As the country progresses towards instituting these, it will be crucial that researchers explore their impact on practices, outcomes, and patient experiences. Finally, it is notable that so few of the included studies considered the quality or safety of infertility care. Healthcare quality and safety has emerged as a key priority of health research⁹², and is particularly relevant within the provision of care by private service providers and in the absence of legislation. Accordingly, future research that comprehensively assesses the quality and safety of infertility care is imperative.