Health professionals require more defined protocols, better funding and patient resources to support couples with recurrent pregnancy loss.

The aim of this study was to explore the practice behaviours, knowledge and attitudes of HPs who see women and their partners with RPL including their prescribing practices of folate and testing recommendations for either partner. The study also investigated HPs interest in and requirements for change to existing recommendations should they be required. This study was a national cross-sectional survey which assessed HPs recommendations, testing, prescribing and referral practices when providing care to women with RPL and their reproductive partners. The survey questions were structured around the existing recommendations for HP’s by Australian 54 – 56 and International guidelines 57 , 58 . The HPs were asked about their recommendations to women and men in relation to preconception health using a scale of ‘never’, ‘sometimes’ or ‘always’. Data were collected from 11th October 2023 until March 2024. The survey link was emailed to members of the following Associations for distribution – Royal Australian College of General Practitioners (RACGP), the Australian College of Midwives (ACM), the Fertility Society of Australia (FSA) and the Perinatal Society of Australia and New Zealand (PSANZ), administered online using Qualtrics software, Version XM October 2023 59 . HPs were eligible to participate if they were able to read English and were an Australian based health professional in current clinical practice and provide care to women and their reproductive partners with RPL. The survey consisted of thirty-three questions with adaptive questioning for sixteen of the questions. The time frame to complete the survey was approximately ten minutes. Respondents were able to review and change their answers (through a back button). A prize draw of a $200 book voucher was offered to participants should they wish to participate and if they opted in, they were directed to a second survey that collected their email address and name to ensure response anonymity was maintained. Pilot testing and consultation of the survey questions was conducted with the association representatives from the RACGP, ACM and PSANZ. The survey design applied the RE-AIM framework 60 to evaluate the potential for public health and population impact. The RE-AIM framework includes five dimensions: reach , effectiveness , adoption , implementation and maintenance 60 . These dimensions assist researchers in program planning, implementation, evaluation and reporting for health research 61 . The framework was employed to understand the views of HPs towards the use of multivitamins, the recommendations and testing procedures they follow for patients with RPL. The key outcomes were to determine who are considered to be the front line professionals that treat and support patients with RPL, evaluate the issues that are meaningful to the practitioner, i.e.: do they feel they have the resources they need to assist women who experience RPL and to understand that if changes were warranted, would they participate and implement the changes. If so, are there any barriers to implementing these changes? The survey instrument included five key sections: practitioner characteristics; preconception health care – protocols; prescribing and testing; folate prescribing, dosing and use; RPL - protocols, prescribing and testing; and resources and guidelines for clinical management of RPL. Ethics approval was received from the University of Technology Human Ethics Committee (Approval no. ETH23-8411). This study was conducted in full accordance with the ethical principles outlined in the Declaration of Helsinki, including its most recent amendments, which emphasize respect for individuals, the right to self-determination, and the importance of informed consent. All participants were provided with detailed information about the study’s purpose, procedures, and their rights, and gave explicit informed consent before participating. No personally identifying data were collected during the survey, except in instances where participants voluntarily provided contact details for the sole purpose of entering a prize draw. Such information was stored separately and was not linked to survey responses in any way. STATA software version 18 (2023) 62 was used to complete the analysis. The data were cleaned and coded in excel prior to input into Stata. Missing responses were excluded from analysis and frequencies and percentages for all categorical data were prepared.

There were 175 responses to the survey, however after data cleaning eight respondents failed to start the survey, 19 were incomplete and nine responses said no to the screening question. This resulted in a total of 139 valid responses for analysis. The characteristics of the respondents are outlined in Table  1 . The HPs that responded to the survey were from QLD ( n  = 44; 32%), NSW/ACT ( n  = 40; 29%), VIC ( n  = 24;17%), SA ( n  = 12; 9%) WA ( n  = 13; 9%), and TAS ( n  = 2, 1%) (data not shown). Over half the respondents (55.4%) were aged between 40 and 59 years. The respondents were predominantly female (86.3%). GP’s comprised the largest professional group (25.9%) followed by midwives (23.5%). Gynaecologists and obstetricians each accounted for 15.9% while fertility or IVF specialists comprised 13.5% of the respondents. The majority of respondents had been practicing for more than 21 years (34.5%) and over half the respondents (56.8%) provided care for women with more than two pregnancy losses at least once a month. Only 22.3% of HPs reported providing care to couples with RPL (i.e., three consecutive pregnancy losses) yet over half of those reported providing care for RPL once a month or more (56.8%). Table 1 Characteristics of participants. All ( n  = 139) Participant Characteristics N % Age in years 20–39 40 28.8 40–59 77 55.4 60+ 22 15.8 Gender Male 15 10.8 Female 120 86.3 Non-binary / Prefer not to say 4 2.9 Years in clinical practice Less than 5 years 9 6.5 6–10 years 29 20.9 11–15 years 30 21.6 16–20 years 23 16.5 More than 21 years 48 34.5 Profession General Practitioner 44 25.9 Gynaecologist 27 15.9 Fertility or IVF Specialist (reproductive, endocrinology & infertility) 23 13.5 Obstetrician 27 15.9 Midwife 40 23.5 Other, please specify 9 5.3 Frequency of care Less than once per year 13 9.35 Several times per year 47 33.8 Once a month 19 13.7 Two or more times per month 29 20.9 At least once per week 31 22.3 Characteristics of participants. Participants’ practice behaviours for women with regard to preconception health are presented in Table  2 . The majority of HPs (91.4%) indicated that they ’always’ recommend a prenatal multivitamin containing folate to their female patients. Less commonly, but still reported by more than half of respondents, was ‘always’ recommending patients achieve an ideal body mass index (BMI) (59%), and blood sugar or diabetes control (64.8%). Most HPs also reported ‘always’ recommending their patients follow a healthy diet (80.6%), follow a regular exercise routine (72.7%), and avoid cigarettes, alcohol and recreational drugs (89.9%). They also commonly reported (90.7%) reviewing women’s current health status and medications as part of their assessment, while almost two thirds (63.3%) indicated ‘always’ referring to a specialist when necessary. The practice most identified by participants as ‘never’ being recommended was ‘achieving an ideal BMI’ (7.9%). Table 2 Frequency that health professionals provide recommendations to women and men during preconception. Recommendation Provide recommendations to women ( n  = 139) Provide recommendations to Men ( n  = 69) Never Sometimes Always Never Sometimes Always n % n % n % n % n % n % Prenatal multivitamin containing folate ( n  = 160) 2 1.4 10 7.19 127 91.4 12 57.1 5 23.8 4 19.0 Achieving an ideal BMI ( n  = 160) 11 7.9 46 33.1 82 59 3 14.3 11 52.4 7 33.3 Blood sugar/diabetes control ( n  = 160) 8 5.8 41 29.5 90 64.8 4 19.0 7 33.3 10 47.6 Following a healthy diet ( n  = 160) 3 2.2 24 17.3 112 80.6 1 4.8 5 23.8 15 71.4 A regular exercise routine ( n  = 160) 4 2.9 34 24.5 101 72.7 1 4.8 4 19.1 16 76.2 Evaluation of personal/family history of genetic issues ( n  = 160) 6 4.3 39 28.1 94 67.6 1 4.8 6 28.6 14 66.7 Avoidance of cigarettes, alcohol, and recreational drugs ( n  = 139) 5 3.6 9 6.5 125 89.9 Reduction/elimination of cigarettes ( n  = 21) n/a n/a n/a n/a n/a n/a 1 4.8 3 14.3 17 81.0 Reduction/elimination of alcohol ( n  = 20) n/a n/a n/a n/a n/a n/a 2 10.0 7 35.0 11 55.0 Reduction/elimination of drugs ( n  = 20) n/a n/a n/a n/a n/a n/a 1 5.0 5 25.0 14 70.0 Review of current health status and medications ( n  = 159) 2 1.4 11 7.91 126 90.7 1 5.0 6 30.0 13 65.0 Referral/correspondence with specialist if required ( n  = 160) 6 4.3 45 32.4 88 63.3 0 0 10 47.6 11 52.4 Screening for STIs and other infectious diseases ( n  = 160) 5 3.6 52 37.4 82 59.0 2 9.5 10 47.6 9 42.9 Cervical screening ( n  = 139) 4 2.9 35 25.2 100 71.9 Frequency that health professionals provide recommendations to women and men during preconception. Respondents reported ‘always’ screening for STIs and other infectious diseases (59%), HPV cervical screening (71.9%) and evaluation of genetic issues (67.6%). When asked if there were any other practices, they might recommend that were not listed in the survey, 54% of HPs reported they made no other recommendations, however 46% said they recommended other practices to their preconception patients such as relaxation, checking Rubella vaccinations, mental health evaluations and cycle tracking. When asked about consulting with the male reproductive partner for a dedicated preconception visit (Table  2 ) 41% of HPs reported that they do not include the male partner in a dedicated preconception visit, while only 11% reported they consistently do so. 19% of respondents reported ‘always’ prescribing a multivitamin containing folate to the male partner, while 57% of HPs said they ‘never’ recommended one. Achieving an ‘Ideal BMI ‘ for men was recommended ‘sometimes’ (52.4%), while 33.3% of HPs stated they ‘always’ recommend an ‘ideal BMI’. Blood sugar management was reported as ‘always’ prioritised by 47.6% of respondents, with an additional 33.3% said they ‘sometimes’ prioritise blood sugar management. So too, a healthy diet was stated as being strongly recommended, with 71.4% stating they ‘always’ recommend a healthy diet as well as a regular exercise routine (76.1%). Assessment for genetic issues was reported being ’always’ recommended by 66.7% of respondents. The recommendation to avoid cigarettes (80.9%), reduce alcohol (55.0%) and avoidance of drugs (70.0%) was not reported to be recommended as much for men as women, nor was the screening for STI’s and other infectious diseases (42.9% for men versus 59.0% for women) (Table  2 ). Most respondents (68.2%) reported recommending multivitamins only for women (Table  3 ), while 31.8% reported they suggest multivitamins for both partners. For those HPs that do recommend a multivitamin, 59.9% reported they commenced the multivitamin three to four months before attempting to conceive, while 12.1% recommended starting two months before, and 14.4% one month prior. A small percentage (5.30%) reported that they advise commencing the multivitamin when the woman is actively trying to conceive, with 8.3% reporting they provide other specific timings such as on cessation of contraception, once pregnant or at their first consultation. Table 3 Prescribing behaviours regarding folate and multivitamin use for men and women experiencing fertility issues. Participants ( n  = 132) % Patient group prescribed prenatal multivitamin Only to women 90 68.2 To both men and women 42 31.8 Stage for commencement of multivitamin Three to four months before trying to conceive 79 59.9 Two months before trying to conceive 16 12.1 One month before trying to conceive 19 14.4 When trying to conceive 7 5.3 Other, please specify 11 8.33 Length of time to take multivitamin For first trimester 37 18.9 Second trimester 3 1.5 Third trimester 4 2.0 Throughout the whole pregnancy 89 45.4 Breastfeeding 50 25.5 Other, please specify 13 6.6 Multivitamin Products Commonly Prescribed Bayer Elevit 61 31.9 Bioceuticals In Natal 14 7.3 Blackmores Pregnancy & Breastfeeding Gold 48 25.1 Blackmores iFolic 23 12.0 Patients Own Choice 16 8.4 Swisse Prenatal 2 1.0 Eagle Tresos B 2 1.0 Other 25 13.1 Form of folate in the multivitamin Folic acid 115 80.9 Folinic acid 13 9.2 Methyl folate 11 7.7 Don’t know 3 2.1 Change of folate prescription in case of RPL No change 69 67.6 Increase the dose of folate 18 17.6 Reduce the dose of folate 1 1.0 Change the folate type 3 2.9 Stop the use of a folate supplement 1 1.0 Other, please specify 10 9.8 Awareness of the practice of prescribing 5 mg of FA for women with RPL No 46 46.9 Yes 35 35.7 Not sure 17 17.4 Frequency prescribing 5 mg of folic acid to a woman with RPL Never 3 8.6 Sometimes 12 34.3 About half the time 1 2.9 Most of the time 8 22.9 Always 11 31.4 Prescribing behaviours regarding folate and multivitamin use for men and women experiencing fertility issues. For the duration of multivitamin intake, 45.4% HPs stated they recommend use throughout the entire pregnancy, and 18.9% recommend taking the multivitamin for the first trimester only. Additionally, 25.5% of HPs responded they suggest continued use of multivitamins during breastfeeding, with few specifically advising the second (1.5%) or third (2.0%) trimesters. Bayer Elevit® was reported as the most commonly prescribed prenatal multivitamin (31.9%), followed by Blackmores Pregnancy & Breastfeeding Gold (25.1%), Blackmores iFolic (12.0%) and Bioceuticals In Natal (7.3%). The form of folate reported being prescribed most often was folic acid (80.9%). 68% of HPs reported not changing the folate prescription when a woman experienced RPL, and 17.6% reported they increased the dose of folate if their patient had a pregnancy loss. A small percentage reported reducing the dose (1.0%) or changed the form of folate (2.9%) following RPL. Some respondents also reported recommending stopping the use of folate supplements (1.0%) or checking for MTHFR polymorphisms and homocysteine. HPs were asked how frequently they undertake certain investigations when providing care to a woman with RPL (Table  4 ). The tests and screening reported most commonly by participants as ‘always’ requested for RPL were thyroid function testing (82.4%), antibody testing (76.9%), routine antenatal screening (70.3%), glucose metabolism testing (65.2%) and Polycystic Ovarian Syndrome testing (PCOS) (52.4%), acquired thrombophilia (such as Antiphospholipid syndrome, anticardiolipin, lupus antigen) (53.9%), congenital thrombophilia (such as FVL, prothrombin, anti-thrombin, protein C/S) (32.5%) and bacterial vaginosis (25.6%). Referral to another practitioner was recommended by 73.0% of respondents. The tests and screenings most commonly reported as ‘never’ being requested by respondents were natural killer cell activity (85.1%), paternal sperm DNA fragmentation index (67.8%) and investigation of paternal BMI (47.13%). Table 4 Investigations and screenings for women and their partners following RPL. never sometimes always n % n % n % Investigations for women with RPL Cytogenic analysis of products of conception 31 36.9 17 20.2 36 42.9 Peripheral maternal blood karyotyping 26 32.5 17 21.3 37 46.3 Peripheral paternal blood karyotyping 34 42 13 16.1 34 42.0 Leiomyoma 38 43.7 13 15.0 36 41.4 Mullerian anomalies 37 44.1 7 8.3 40 47.6 Uterine synechiae (Asherman’s) 35 43.2 17 21 29 35.8 Thyroid function 7 8.2 8 9.4 70 82.4 Glucose metabolism 12 13.5 19 21.4 58 65.2 PCOS 11 13.1 29 34.5 44 52.4 Progesterone levels 23 29.9 23 29.9 31 40.3 Prolactin levels 26 30.2 25 29.1 35 40.7 HLA typing 64 82.1 11 14.1 3 3.9 NK cell activity 74 85.1 12 13.8 1 1.2 Paternal sperm DNA fragmentation index 59 67.8 20 23.0 8 9.2 Investigate paternal BMI 41 47.1 22 25.3 23 26.4 No tests - Refer to another practitioner 27 27.0 42 42.0 31 31.0 Screening tests for women with RPL Congenital thrombophilia 34 29.1 45 38.5 38 32.5 Acquired thrombophilia 19 16.2 35 30.0 63 53.9 Bacterial vaginosis 27 23.1 60 51.3 30 25.6 Chlamydia 12 10.3 51 43.6 54 46.2 Paternal smoking 23 19.7 31 26.5 63 53.9 Paternal alcohol intake 26 22.2 38 32.5 53 45.3 Paternal illicit substance use 27 23.1 34 29.1 56 47.9 Further tests for either male or female following RPL Male Karyotype 14 21.5 11 16.9 40 61.5 Female Karyotype 13 20.0 10 15.4 42 64.6 Ultrasonography 8 12.3 8 12.3 49 75.4 Sono hysterography 11 25.0 21 47.7 12 27.3 Thyroid function tests & Antibodies 6 9.2 9 13.6 50 76.9 Acquired thrombophilia screen 5 7.7 14 21.5 46 70.8 Antenatal screen 6 9.4 13 20.3 45 70.3 Products of conception: Karyotype & histopathology 10 15.9 15 23.8 38 60.3 Blood tests 7 11.1 7 11.1 49 77.8 Sperm testing 21 32.8 16 25.0 27 42.2 Blood testing 10 17.2 12 20.7 36 62.1 None, I refer 22 42.3 16 30.8 14 26.9 Referral Strategies for those that refer Refer to relevant support group 4 5.0 49 61.3 27 33.8 Refer to a psychologist/counsellor for further support 0 0.0 50 62.5 30 37.5 Speak to them myself to understand how they are feeling and lend support 0 0.0 18 22.5 62 77.5 Refer to another professional 5 6.3 61 76.2 14 17.5 Investigations and screenings for women and their partners following RPL. For the male partner, HPs responded that the screenings they focused on were lifestyle practices such as smoking (53.9%), illicit substance use (47.9%) and alcohol intake (45.3%). In the survey, respondents were asked about their practices for managing RPL and the strategies they might employ to support patients (Table  5 ). The majority of HPs reported that they would primarily review diet and lifestyle strategies like smoking and alcohol intake (82.5%) and caffeine intake (39.5%), ensure patients maintain a healthy BMI (75.4%) and conduct further testing and investigations (77.2%) and prescribe prenatal multivitamins (70.2%). Psychological support was reported as being an important consideration with 82.5% of HPs ‘always’ referring for emotional support. The HPs reported that they predominantly speak to the patient themselves to understand how they are feeling and lend support where they can (77.5%) ’always’ or ‘sometimes’ (22.5%). Some HPs referred patients to a psychologist or counsellor for further support, ‘sometimes’ (62.5%) or ‘always’ (37.5%). The majority of HPs ‘sometimes’ (76.5%) refer patients to other professionals, and some ‘always’ (17.5%) refer. Only 6.25% ‘never’ refer patients to other professionals (Table  5 ). 57% recommended continuing attempts to conceive (57%). Table 5 Strategies used and resources required by health professionals to support couples with recurrent pregnancy loss (RPL). Participants ( n  = 139) n % Strategies employed by health professionals if patients experience RPL* Refer to another specialist/centre 74 11.3 Prescribe a prenatal multivitamin 80 12.2 Advise them to continue attempting to conceive 65 9.9 Further investigations & testing for either reproductive partner 88 13.4 Recommend medications, please specify 27 4.1 Review diet and lifestyle strategies (i.e., smoking and alcohol) 97 14.8 Ensure they maintain a healthy body mass index 86 13.1 Restrict caffeine intake 45 6.9 Referral for emotional support 94 14.3 Resources required by health professionals to best support individuals with RPL* Guidelines & protocols to follow 89 21.2 General Patient Resources 75 35 Handouts/information for men and women 71 16.9 Dosing charts and information for HPs 54 25.2 Referral information for support groups 52 12.4 Improved funding to ensure specialised preconception appointments 48 11.4 Recommendation of products and where they can be purchased 42 19.6 More specialised training in this area 44 10.5 Better referral networks 42 10.0 Pricing of the recommended products 36 16.8 Improved funding to ensure a timely appointment with a specialist 39 9.3 More access to midwives for women with RPL 33 7.9 Other, please specify 2 0.5 *Participants could select more than one response. Strategies used and resources required by health professionals to support couples with recurrent pregnancy loss (RPL). *Participants could select more than one response. HPs were asked if they feel they have access to the necessary resources (Table  5 ) to support couples with RPL and 58.1% felt they either definitely or probably have access to sufficient resources, however, 34.4% felt they ‘definitely’ did not or ‘probably’ did not have the resources to support patients with RPL. On the other hand, 7.5% were unsure. Overwhelmingly HPs identified meta-analysis of primary research as considered extremely important (82.8%) or moderately important (10.8%) evidence for them to change their practice behaviours, with (6.45%) rating it as not at all important. Randomised clinical trials were the second most important research study type with respondents rating them as extremely important (77.4%) or moderately important (16.1%) with 6.45% deeming them not at all important. Observational studies were considered by participants to be moderately important (64.5%), not at all important (21.5%) and extremely important (14.0%) while case reports were rated moderately important (43.0%), not at all important (41.9%) and extremely important (15.1%). Table 6 Health professionals’ perceptions regarding access, importance and influence of resources and research evidence for management of RPL. Perceived level of access to resources and research evidence required to amend protocols for management of RPL Definitely not n (%) Probably not n (%) Might or might not n (%) Probably yes n (%) Definitely yes n (%) 11 (11.8) 21 (22.6) 7 (7.5) 36 (38.7) 18 (19.4) Types of research required by health professionals for them Not at all important n (%) Moderately important n (%) Extremely important n (%) Case reports 39 (41.9%) 40 (43.0%) 14 (15.1%) Observational study 20 (21.5%) 60 (64.5%) 13 (14.0%) Randomised Control trial 6 (6.5%) 15 (16.1%) 72 (77.4%) Meta-analysis of primary research 6 (6.5%) 10 (10.8%) 77 (82.8%) Other 47 (50.5%) 30 (32.3%) 16 (17.2%) Influential sources for RPL Management None at all n (%) A moderate amount n (%) A great deal n (%) International clinical guidelines 9 (9.8%) 38 (41.3%) 45 (48.9%) National clinical guidelines 2 (2.3%) 25 (28.4%) 61 (69.3%) Recommendation from a peer 15 (16.3%) 62 (67.4%) 15 (16.3%) Feedback about response to treatment from a patient 21 (22.8%) 49 (53.3%) 22 (23.9%) New research evidence 4 (4.4%) 43 (47.3%) 44 (48.4%) Your own clinical observations 11 (12.0%) 59 (64.1%) 22 (23.9%) Health professionals’ perceptions regarding access, importance and influence of resources and research evidence for management of RPL. Not at all important n (%) Moderately important n (%) Extremely important n (%) None at all n (%) A moderate amount n (%) A great deal n (%) When asked what resources HPs would require to implement a change in recommendations to their patients, should the appropriate research be provided, the establishment of guidelines and protocols to follow was the most commonly chosen response (95.7%). Handouts and information for both men and women were reported as being crucial, with 87.2% of respondents advocating for patient educational resources for both men and women. HPs would like dosing charts and information on products like multivitamins (62.8%), what they cost (41.9%) and where they can be purchased (48.8%). Other recommendations HPs reported as necessary included the need for more specialised training (47.3%), improved funding to ensure timely and specialised preconception appointments (51.6%) and specialised preconception appointments with a specialist (41.9%), and better referral networks (45.2%). Additionally, respondents expressed the need for increased access to midwives for the women with RPL (35.5%) and also mentioned improved referral information for support groups (55.9%). One practitioner commented that ”research is vital” in this area and another stated that “this is a confronting issue for both HPs and patients and definitely more resources are required”. For the clinical management of patients with RPL the most influential source for decision making (Table  6 ) and management of these patients were national clinical guidelines with most reporting it had a great deal of influence (69.3%) and a moderate amount of influence (28.4%). International guidelines (48.91%) and new research evidence (48.35%) were also reported as important with clinical observations (23.9%), feedback from a patient (23.9%) and recommendations from a peer (16.3%) less so.

The rate of pregnancy loss (defined as the spontaneous loss of pregnancy before 24 weeks gestation) 1 in Australia is similar to that of other countries with 10–19% of women experiencing a pregnancy loss. Recurrent pregnancy loss (RPL) is estimated to affect 1% of couples 2 , 3 , however it is now presumed to be closer to 5% 4 . RPL has traditionally been defined as three or more pregnancy losses in a row 5 , however it is more commonly defined as two or more pregnancy losses prior to 24 weeks gestation by the American Society for Reproductive Medicine (ASRM) 6 and the European Society for Human Reproduction and Embryology (ESHRE) 7 and in Australia it is defined as two or more pregnancy losses prior to 20 weeks gestation 8 . The pooled risk of pregnancy loss has been found to be 15.3% of all recognised pregnancies which equates to around 23 million pregnancy losses before 24 weeks gestation each year 9 , however, it is believed to be much higher if preclinical pregnancy losses are included 10 . These numbers are hard to pinpoint because pregnancy loss is not typically reported 9 , 11 – 13 . According to the Australasian recurrent pregnancy loss clinical management guideline 2024, the evaluation and management of RPL may include assessment of several risk factors. These include maternal age at conception, antiphospholipid syndrome (an acquired thrombophilia), environmental and lifestyle factors (such as chemical exposures and stress), male factor issues, uterine abnormalities and endocrine disorders (such as thyroid dysfunction, hyperprolactinemia, polycystic ovarian syndrome (PCOS), obesity, glucose intolerance and progesterone deficiency), autoimmune conditions and inflammatory causes (such as endometritis and adenomyosis). Additionally, a significant proportion of cases are classified as “unexplained loss” with chromosomal aneuploidy being the most common cause) 2 , 8 . Until recently, there were no Australian guidelines or protocols for health professionals (HPs) to support couples with RPL, and clinical practice was largely informed by international recommendations 14 . These earlier guidelines advised evaluation of chromosomal and anatomical anomalies, thrombophilias, endocrinological disorders, infection, immune system disorders and environmental and lifestyle factors 14 . This gap in the Australian landscape was addressed in June 2024 with the release of the Australasian Recurrent Pregnancy Loss Clinical Management Guideline 2021, Parts 1 and 2, developed by the Australian Certificate of Reproductive and Endocrinology and Infertility (CREI) consensus Expert panel 8 , 15 . Part 1 focuses on chromosomal factors and anatomical factors of the uterus and/or cervix, endocrine risk factors including thyroid disorders and hyperprolactinemia, polycystic ovarian syndrome (PCOS), obesity, glucose intolerance and progesterone deficiency 8 . Part 2 addresses acquired thrombophilia, autoimmune conditions, inflammatory and endometrial causes (endometritis), environmental and lifestyle factors (for example, environmental exposures, stress), male factor issues (such as sperm aneuploidy) and unexplained RPL 15 . Unexplained pregnancy loss (UPL) accounts for an estimated 50–75% of all RPL cases 4 . These new guidelines do not include any recommendations regarding multivitamins, folate dose or the form of folate, despite folic acid being considered one of the most important nutrients for women to take during the periconception period (encompassing three months before and three months after conception) 16 . Folate is required for DNA synthesis 3 and is regulated by the gene methylenetetrahydrofolate reductase (MTHFR) 17 . Research suggests a potential association between MTHFR gene polymorphisms and unexplained infertility 18 , 19 . Several studies found increased frequencies of MTHFR variants in individuals with unexplained infertility compared to controls 18 , 20 , 21 . The MTHFR C677T polymorphism has been associated with unexplained infertility in women 20 – 22 and the A1298C polymorphism has been linked with male infertility 19 , 23 – 25 . Some studies also observed connections between MTHFR mutations and RPL 26 – 29 . Studies involving men 30 and women with MTHFR polymorphisms have shown improved pregnancy outcomes when the sample population are supplemented with 5-methyltetrahydrofolate (methyl folate) rather than folic acid 31 – 33 . A recent case series identified that women with infertility had greater pregnancy outcomes when folic acid was replaced with methyl folate and the dose of folate was increased beyond the recommended 500 mcg 34 . New evidence suggests that not everyone requires the same form and dose of folate, and a more nuanced approach may be appropriate 35 – 43 . Preconception health care is crucial for women and men who are planning to conceive. It involves a variety of recommendations and practices to ensure the best possible health outcomes for both the mother and the baby. Previous interviews with health professionals (HPs) in Australia indicate low awareness of preconception health care, missed opportunities and confusion about responsibility for preconception care 44 . Many HPs have a role in supporting women and couples in preconception and pregnancy. General practitioners (GPs) are considered ‘the first line’ contact and are well placed through their primary care role to deliver the majority of preconception care, yet a 2013 study of Australian GPs reported that GP’s lack the necessary time, resources and training to effectively provide adequate preconception care 45 , with a later study identifying that only 54% of GPs were aware of the preconception guidelines even though they consider it their responsibility to give preconception care advice 46 . The findings of these previous studies were supported by further research in which women who wanted to become pregnant reported a lack of information about preconception care, including the use of preconception multivitamins 46 . Approximately three quarters (74%) of women report asking preconception advice from their GP 47 yet research suggests that a lack of knowledge about safety of multivitamins and nutrients may stop the GP prescribing these multivitamins 48 . Women see their obstetrician or gynaecologist once they are pregnant unless they have RPL or infertility issues in which case they may receive preconception advise from their obstetrician or from a multidisciplinary HPs network 49 . Midwives also provide care to women, typically once they are pregnant, but they do not routinely offer preconception care 49 despite having interest in providing pre- and interconception care, claiming that low prioritisation in service planning is the key barrier to providing such care 50 . A recent Australian study found a high degree of variability in the HPs’ recommendations regarding preconception care, and evidence that HPs lacked awareness of existing preconception practice guidelines 51 . The HPs stated they require more patient information, more training and resources, more consultation time and improved referral networks 51 . Fertility specialists face challenges in providing evidence-based investigations and treatments due to a lack of high-quality clinical trials 52 . The complexity of RPL research has resulted in calls for improved methodologies and consideration of epidemiological factors 52 , 53 . Therefore, it is important to understand the barriers and readiness of HPs to adopt different interventions and explore the strategies they employ to support couples with RPL.

RPL needs to be a key priority. Men provide 50% of the DNA to the embryo, yet no assessment of sperm quality or the nutrients that support spermatogenesis like folate are prescribed. Men are largely omitted from the preconception and RPL picture. Practitioners require better resources, more funding for appointments to support couples with RPL and protocols with dosing recommendations for folate. They require more support for couples physically and emotionally. There is a need for revised recommendations that include men and folate prescribing for both men and women. Unexplained infertility needs to be explained.

This survey of HPs’ practice behaviours in the management of RPL identified findings that have broad implications for reproductive health care as well as specific insights for RPL management. Firstly, males are often being excluded from preconception health care even though they provide 50% of DNA to the embryo. Secondly, couples experiencing RPL require support, as do the HPs supporting them. There is a need for improved and updated recommendations and protocols that include folate prescribing and dose, improved funding and training for HP’s and better resources for couples experiencing RPL. Thirdly, folate is an integral part of preconception care, not only to prevent neural tube defects but to support DNA methylation critical for oogenesis and spermatogenesis. Recommendations for RPL exclude folate and genetic testing for genes that affect folate metabolism. This study highlights that HPs require more defined protocols for RPL. They feel that they require further education, more funding and more patient resources to help them better support couples experiencing RPL. Although the HPs are following the typical testing procedures as defined by the Australian RPL recommendations 63 they do require more detailed clinical guidelines and protocols to follow which is consistent with a variety of reviews that have evaluated clinical practice guidelines and found them conflicting, lacking in good quality evidence and involvement of those who experience RPL 64 – 67 . A lack of resources for both patients 68 , 69 and HPs constrains how RPL is defined and treated 70 , 71 . The current guidelines for RPL are insufficient and there is a call for more evidenced based studies 9 , 67 , 72 , 73 . Research highlights that over 75% of pregnancy losses are deemed ‘unexplained’ 4 , 65 essentially meaning that no cause can be found. How can clinical guidelines be effective if they do not explore the possible cause of up to 75% of pregnancy losses? Reasons for these idiopathic RPLs may be associated with HLA immune factors 74 , 75 , thrombophilia 76 , endocrine and chromosomal abnormalities in greater than 50% of cases 75 , 77 , 78 . Epigenetics plays an important role in RPL through the regulation of key genes influencing DNA methylation and epigenetic modifications 78 . The causes of RPL therefore, such as chromosomal disorders, immune and endocrine dysfunction may well be related to disturbed methylation because of its critical role in maintaining the epigenetic modifications that affect these processes during spermatogenesis and embryonic development 79 – 85 . Studies show that DNA methylation is critically important for the epigenetic patterns and expression of genes that affect spermatogenesis and male reproductive organ development, as it is for women and oogenesis 79 , 81 , 83 , 84 , 86 – 89 . MTHFR genes that affect methylation contribute significantly to spermatogenesis, or rather lack thereof 23 , 36 , 90 – 98 , embryo implantation, growth and development, and abnormal immune balance 78 and it may be time to investigate this further 79 , 85 , 99 . This study highlighted the lack of testing for MTHFR polymorphisms. Numerous reviews highlight the importance of this gene in folate metabolism and fertility, particularly in males 18 , 19 , 23 , 35 , 81 , 94 , 100 – 104 . The lack of association between MTHFR and fertility is due to the fact that much of the research only considers the MTHFR gene in relation to hyperhomocysteinemia 105 – 107 . The discussion should focus on MTHFR in relation to its ability to produce methyl folate and the influence this has on DNA methylation which affects oogenesis and spermatogenesis. Consistent with the views of the HPs in this study, there is a united call for good quality evidence based research and new strategies for unexplained RPL 9 , 65 , 67 , 72 , 73 . The survey highlighted that only one third of HPs felt they had the necessary resources to support couples with RPL. Over half the HPs reported requiring support groups for their patients which reflects one of the biggest issues patients with pregnancy loss face - the lack of emotional support and the minimisation of the psychological effect with a focus on the physical aspect of the loss 13 . Although four out of five HPs in this study stated they refer their patients who experience RPL for emotional support, they predominantly speak to patients themselves to understand how they are feeling and lend support where they can. A significant number recommend continuing attempts to conceive. This is consistent with research that shows in the medical model, support is aimed at a women’s physical recovery and not the emotional support 13 , 108 . Women who experience pregnancy loss are left with feelings of grief for some time and do not feel supported enough by social and health care networks 13 and feel ‘rushed’ to get over it 69 when in reality it may take up to a year for anxiety and depression to be resolved 109 and the woman to recover from the grief 110 . Men also require psychological support but given they are not included in this aspect of fertility care, they often feel left out and the impact on them of RPL is unacknowledged 111 . Doctors and specialists may be willing to provide initial emotional support but they do not have the training, resources or time to provide ongoing care 108 and often it is the next pregnancy and the first 20 weeks where patients feel unsupported 68 . The HPs in this study clearly acknowledge the need for more support for their patients experiencing RPL, asking for more timely appointments with a specialist, dedicated preconception appointments and greater access to midwives. Midwives do not necessarily see patients until they reach 20 weeks gestation 112 and if women do have early pregnancy problems they are more likely to present to their general practitioner or the Emergency department where support is limited 108 . Some hospitals have early pregnancy assessment services staffed by a midwife or nurse, but these are not in many locations and there is a lack of awareness amongst couples experiencing RPL that these exist 108 , 113 . Therefore the call for more access to midwives seems warranted as research shows that midwife support is important in the psychological health of women and their partners with RPL 114 . Following a pregnancy loss, couples want to understand why it happened, what they can do to prevent miscarriage happening again and what tests can be done to find out the cause 10 , 111 . A delay or inability to find a cause increases trauma 66 . For a couple to be told their RPL is ‘unexplained’ is not helpful and very disempowering. There is a need to better identify ways to evaluate the ‘unexplained’ RPL and offer support to these couples. This study highlights that there is little consistency in the prescribing of folate for women and most HPs do not prescribe folate to males in preconception or in the context of RPL. Although women are prescribed a FA-containing multivitamin most of the time, there is no consistency in the amount given and rarely does the prescription change if a woman miscarries. This is reflective in the results of the survey that highlight the HPs need for prescribing and dosage recommendations for folate to support couples experiencing RPL. The worldwide recommendation for preconception for women ranges from 400-600mcg in Australia 56 , 115 , 800mcg in the United States 116 – 118 and 1,000mcg in Canada 119 – 121 . The HPs predominantly recommended Bayer Elevit® (800mcg folic acid) and Blackmores Pregnancy and Breastfeeding Gold® (500mcg FA) and Blackmores I-Folic® (500mcg FA) with over 80% recommending FA over other forms of folate. Even though emerging research is showing that women who take a prenatal multivitamin containing FA in preconception and pregnancy in countries who have FA fortification programmes are exceeding the upper dose deemed safe 122 , HPs are not heeding this warning. Excess FA has been linked with endocrine and hormonal issues 123 , gestational diabetes 124 – 127 and placental development 128 . Guidelines for FA need to discuss the potential for excess levels, particularly in countries like Australia, with both mandatory and voluntary fortification programmes. HPs in this study are largely unaware that alternate forms of folate exist outside folic acid, even though research highlights that other forms of folate may be more effective in cases of RPL, particularly when MTHFR polymorphisms are present 129 . An important finding of this study is the lack of attention males are given in preconception health planning. Our data highlights that no dedicated appointments for the male partner are being undertaken, even though Australian statistics report an estimated 40% of all infertility can be attributed to male reproductive function 130 . Other regions around the world report a similar finding 131 and male infertility may be contributing to as much as 70% of all infertility cases 86 . Research regarding men and infertility is scarce due to a lack of research in this area. Most papers on RPL focus on the female 132 – 135 which was highlighted in a 2016 scoping review that reported only 11% of papers included male participants 134 . This is reflected in the fact that Australian 54 – 56 and international 57 , 58 recommendations and guidelines put sole emphasis on the female. This is despite research highlighting that sperm concentration, quality and pregnancy rates are improved by folate 136 , 137 and micronutrient supplementation 138 – 140 . It was evident from the survey that even after RPL, HP’s conduct little testing for the male partner, with sperm testing conducted by less than half the practitioners, which is consistent with the clinical guidelines that largely ignore the impact of male factor on RPL 141 . Recent research highlights the importance of including male factor issues like DNA fragmentation testing into RPL guidelines 142 . Based on the above, recommendations for males need to be standard care to improve pregnancy outcomes and all guidelines and assessment tools for HPs to support male fertility are warranted 143 , 144 . The strength of this study lies in the national approach inviting participation from fertility health professionals across all sectors of the fertility landscape in Australia. The key limitation is the sample size. Convenience sampling techniques have limitations in that responses from individuals with distinct views on this topic may have been obtained and may not be reflective of the target population, limiting the generalisability of our findings. Those that responded may feel stronger towards this topic than those that did not and therefore there is the potential for non-responder bias. However, the heterogeneity of responses across all fertility specialists suggests that this may have been limited.