Minjeur M et al., 2026·Journal of Restorative Reproductive Medicine
Infertility is a clinical condition that is recognized by the symptom of an inability to conceive through sexual intercourse or to sustain a pregnancy, with that symptom indicating underlying male and/or female pathology.
This definition of infertility was developed through a structured, consensus-informed process involving broad stakeholder engagement. Initially, multiple definitions currently used by various medical professional organizations were reviewed, and a definition document was drafted and submitted to the Board of Directors of the International Institute for Restorative Reproductive Medicine (IIRRM). All IIRRM members were invited to provide feedback on the draft. Approximately 2,500 individuals and 44 organizations from 92 countries were then invited to review the proposed document, representing clinical, scientific, patient, policy, and advocacy perspectives. Submitted comments were reviewed thematically, with suggested revisions evaluated for clarity, clinical relevance, inclusiveness, and consistency with contemporary restorative reproductive medicine. Following this review, 3 substantive changes, 18 minor changes, and 15 citation corrections were incorporated into the final draft which resulted in a revised definition intended to better reflect the medical, social, and practical realities of modern infertility evaluation and care. Final approval by the IIRRM Board of Directors was unanimous.
History of the Discipline · Origins of Restorative Practice
Boyle P, 2025·J Restorative Reprod Med·
Open Access
Recently, editorials have been published in reproductive medical journals that have misunderstood and misrepresented the origin and meaning of “restorative reproductive medicine” (RRM).1,2 This term was first used in 2000 when a group of physicians established the International Institute for Restorative Reproductive Medicine (IIRRM, iirrm.org ). I am a founding member and am currently president of the IIRRM.
The IIRRM was founded as a secular, not a faith-based organization. We adhere to time-honoured medical principles to understand and treat underlying factors responsible for infertility. We are always seeking to improve our diagnosis and treatment of those factors, the training of clinicians who offer RRM, and the quality of clinical practice of RRM. We believe that in the clinical realm, in vitro fertilization (IVF) is often offered quickly without sufficient efforts first made to help couples conceive naturally.
IVF was originally developed to treat patients with bilateral tubal occlusion who could not conceive through sexual intercourse. Most patients who undergo IVF today do not have blocked fallopian tubes. Intracytoplasmic Sperm Injection (ICSI) was developed for patients with severe male factor infertility. Most patients who undergo ICSI today do not have severe male factor infertility. Remarkably, the most recent Cochrane review of IVF indicates ongoing uncertainty about whether IVF improves the live birth rate compared to expectant management for previously untreated couples with “unexplained” subfertility.3
I am an active RRM clinician since 1998 and I have treated thousands of couples. When patients present for fertility treatment, I do not ask them what religion, political view, or philosophy they support, because that is irrelevant to people who want a solution for their infertility. If they have a condition that is better treated by IVF, I tell them that at the first appointment. If natural conception is possible with RRM, I explain what is involved and outline the treatment process which can take up to 12 cycles (most often less) to reach a healthy ongoing pregnancy, or a full course of treatment.
RRM honours patient autonomy. We do not seek to prohibit patient access to IVF. Patients seek us out. RRM expands their choices and options. Many of my patients were previously seen in fertility clinics that offer IVF. Patients repeatedly tell me they did not receive the same depth of investigation or non-IVF treatment in the IVF clinics. I recently received these comments from patients, “RRM empowered us in our fertility journey. It provided a personalised approach. We are so grateful.” And “even if we didn’t conceive, we’d never regret trying RRM as my health improved immeasurably…”
The World Health Organization states that “Infertility is a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse”.4 As RRM physicians, we respectfully suggest a slight but essential alteration: “Infertility is a medical condition defined by failure to achieve a pregnancy after 12 months or more of regular sexual intercourse without contraception, which is caused by one or more underlying diseases and conditions involving the male or female reproductive system.” This definition indicates that infertility is not a singular condition to be treated solely by treatments to generate a pregnancy and birth. Rather, it is “a canary in the coal mine” for human health, indicating the need to identify and address underlying health concerns. 5,6
As RRM physicians and clinicians we have training and backgrounds that allow us to treat infertility patients with a focus on treatments and approaches that restore and optimize natural function. The specialty of reproductive endocrinology and infertility has extensive training with a particular focus on IVF and treatments to improve the success of IVF. But we can and should be in agreement to offer patients evidence-based information and treatments that meet the needs and preferences of patients.
Further research is needed and is currently ongoing on patient-relevant questions, such as: How does an RRM evaluation differ in process and results from a fertility evaluation before initiating IVF? How do the outcomes of RRM and IVF compare on multiple levels including live birth rates, premature delivery, patient satisfaction, health improvement, and repeat successful births?7
For the sake of our patients with infertility, let us strive to be objective about the scientific facts, and meet all patients with respect. Surely as we challenge and learn from one another and strive for excellence, the patients will be the ultimate beneficiaries.
Boyle P et al., 2025·J Restorative Reprod Med·
Open Access
Restorative reproductive medicine (RRM) is an emerging approach that can be used to treat infertility. Our goal was to compare RRM to IVF outcomes in 2019.
We conducted a retrospective clinic-based analysis and referenced it against publicly available data from IVF registries, as published by the Centers for Disease Control and Prevention (CDC) or the Society for Assisted Reproductive Technology (SART) in the USA, and the Human Fertilization and Embryology Authority (HFEA), in the UK. Data from 2019 was collected from routine medical records following treatment at one clinic in Dublin, Ireland during 2019. We defined the demographics, diagnoses, and treatments and then calculated the crude percentages of conception, live birth, multiple pregnancy, prematurity, and low birth weight. These results were benchmarked against data reported in IVF databases. 249 couples had at least one RRM consultation, 187 committed to the RRM treatment program and met the inclusion criteria. The average female age for all included patients was 36.4 years and couples were trying to conceive for a mean of 32.2 months. Of the 187 patients/couples who underwent treatment, 28% had a previous live birth, 30% had a previous miscarriage, and 42% had never conceived;19% (35/187) had previously had IVF, 2.3 + 1.6 IVF cycles per couple. Of the 187 couples, 52% (98/187) conceived, 41% (77/187) had a documented live birth. There were 75 singletons and 2 sets of twins, producing 79 babies. Time to conception for live birth patients averaged 12 + 8 months. The average birth weight was 3422g (7lb 9oz) and average weeks’ gestation at delivery was 39 + 1.5 weeks. 4.0% (3/75) of singleton babies were premature (33-37 weeks) and none were very premature (< 32 weeks). 5.3% (4/75) of singleton babies had low birth weight (< 2,500g). When we compared births across age groups, the RRM percentages with live birth were comparable to those in a single cycle of IVF with multiple subsequent embryo transfers, and greater than a single cycle of IVF with a single embryo transfer. Furthermore, RRM babies had fewer multiple pregnancies, and singleton RRM pregnancies had less than half as many premature deliveries compared to IVF, (6.5% RRM all pregnancies or 4.0% RRM, singleton pregnancies vs 14.4% SART, all pregnancies or 11.8% CDC, singleton pregnancies). 74% (26/35) of couples who remained in contact with us and tried for another pregnancy had a repeat successful live birth. In our clinic, a comprehensive RRM assessment and treatment followed by up to 12 optimal cycles of timed intercourse resulted in a 41% live birth rate (crude rate). We propose that using RRM may improve a couple’s chance of having a healthy pregnancy and reduce the demand for IVF. Furthermore, RRM reduces the risk of multiple pregnancy, low birth weight and premature delivery compared to IVF. The majority of couples who sought a second live birth were successful.
Limitations and Future directions: This is a retrospective analysis with a small number of RRM patients, compared to large IVF databases of patients using one cycle of IVF, including all transfers made from the IVF retrieval. While useful for benchmarking, conclusions are limited by sample size, and the lack of relevant prognostic data (other than female age) for the IVF patients. Larger prospective studies with full prognostic data are needed to make a proper comparison of RRM and IVF outcomes.
Boyle PC et al., 2024·Front Med (Lausanne)·
Open Access
Hypoandrogenemia is not usually considered as a potential cause of recurrent miscarriage. We present the case of a 30-year-old female with 6 previous pregnancies resulting in one live birth and 5 pregnancy losses, including fetal demise at 24 weeks gestation. She had standard investigations after her 4th loss, at a specialized miscarriage clinic. Lupus anticoagulant, anticardiolipin antibodies, thyroid function, parental karyotypes were all normal. Fetal products confirmed triploidy for her 4th miscarriage at 16 weeks gestation. She was reassured and advised to conceive again but had fetal demise after 24 weeks gestation. This was her 5th pregnancy loss with no explanation. She attended our Restorative Reproductive Medicine (RRM) clinic in January 2022. In addition to poor follicle function, we found hypoandrogenemia for the first time. Treatment included follicle stimulation with clomiphene and DHEA 25 mg twice daily pre-conception with DHEA 20 mg once daily maintained throughout pregnancy. She delivered a healthy baby boy by cesarean section at 36 weeks gestation in November 2023. Hypoandrogenemia should be considered as a contributory factor for women with recurrent miscarriage or late pregnancy loss. Restoration of androgens to normal levels with oral DHEA is safe and can improve pregnancy outcome.
Boyle P et al., 2024·Frontiers in Reproductive Health
Low serum estradiol in early pregnancy is associated with an elevated risk of miscarriage. We sought to determine whether efforts to restore low blood estradiol via estradiol or dehydroepiandrosterone (DHEA) supplementation would reduce the risk of miscarriage as part of a multifactorial symptom-based treatment protocol. This retrospective cohort study included women with low serum estradiol levels in early pregnancy, defined as ≤50% of reference levels by gestational age. Estradiol or DHEA were administered orally, and the primary outcome measure was serum estradiol level, in reference to gestational age. The secondary outcome measures included miscarriage, birth weight, and gestational age at birth. We found no significant effect of estradiol supplementation on serum estradiol levels referenced to gestational age, while DHEA supplementation strongly increased estradiol levels. For pregnancies with low estradiol, the miscarriage rate in the non-supplemented group was 45.5%, while miscarriage rate in the estradiol and DHEA supplemented groups were 21.2% (p = 0.067) and 17.5% (p = 0.038), respectively. Birth weight, size, gestational age, and preterm deliveries were not significantly different. No sexual abnormalities were reported in children (n = 29) of DHEA-supplemented patients after 5-7 years follow-up. In conclusion, DHEA supplementation restored serum estradiol levels, and when included in the treatment protocol, there was a statistically significant reduction in miscarriage.
Outcomes and Effectiveness · Outcomes by Diagnosis
Restorative reproductive medicine represents a comprehensive approach to subfertility (infertility and miscarriage) with investigations, diagnoses, and treatments combined with fertility charting to restore optimal reproductive function. Restorative reproductive medicine assumes that multiple factors need to be identified and treated (cycle optimization) for up to 12 cycles to achieve a successful pregnancy. Conception can occur during normal intercourse without intrauterine insemination or in vitro fertilization. A 35-year-old Croatian female presented for fertility treatment in May 2019 with a previous diagnosis of polycystic ovaries, infertility of 16 years duration, and 8 unsuccessful embryo transfers with in vitro fertilization and intracytoplasmic sperm injection. She was gravida 3 para 0, with 2 miscarriages after spontaneous conception at 5-6 weeks gestation in 2002 and 2004, followed by a miscarriage after in vitro fertilization at 12 weeks gestation in 2011. We initially found poor follicle function and suboptimal progesterone levels. Restorative reproductive medicine treatment resulted in conception after two cycles of treatment. This pregnancy ended in miscarriage at 7 weeks 4 days. Additional investigations found a balanced Robertsonian translocation (13, 14) and a uterine septum. We achieved repeat fertilization with restorative reproductive medicine after three cycles of treatment following resection of the uterine septum and ovulation induction with letrozole and human chorionic gonadotrophin. She had a full-term healthy pregnancy and live birth in 2021. We propose that a full evaluation of underlying factors, and up to 12 cycles of cycle optimization, should be offered to subfertile patients before considering in vitro fertilization treatment.
Golianovskyi OV et al., 2020·Reproductive Endocrinology·
Open Access
There are still many complex issues in the management of autoimmune pathologies in gynecology and reproductology, endometriosis in particular. Naltrexone, a competitive antagonist of opiate receptors in the central and peripheral nervous systems, reveals new qualities such as effects on autoimmune processes. Naltrexone in low doses of 1.7–5 mg (Low Dose Naltrexone, LDN) revealed the opposite effect on opiate receptors in the form of a rebound effect and, as a consequence, a strong increase in endogenous endorphins and enkephalins. Studies of elevated levels of these neurotransmitters have provided evidence of a multidisciplinary beneficial effect on the immune system of people with endorphin and enkephalin deficiency, an association between the endogenous opiate system and cells and tissue growth in general and healthy immune function was confirmed. The most explored effects of them are such as blocking the synthesis ofpro inflammatory cytokines IL-6, IL-12, tumor necrosis factor, the effect on neuroglia through toll-like receptors, the effect on the cycle cells growth, especially malignant tumor cells, through interaction with opiate growth factor, modulation synthesis of T- and B-lymphocytes. Growing evidence of LDN efficacy is becoming a potentially effective clinical practice in autoimmune pathologies, but still off-label used.Some data of clinical trials is presented. Four studies with Crohn's disease with results of relief of symptoms and remission, including experience in pediatrics. Three clinical trials with LDN results in multiple sclerosis with improved quality of life and improved symptoms. The scientific hypothesis suggests the success of LDN due to the reduction of induced nitric oxide synthase activity. The success of management of patients with malignant tumors is also presented. The article contains the latest data from clinical trials on reported serious and non-serious side effects of naltrexone at various doses, including data confirming the safety of taking mid-therapeutic naltrexone doses throughout pregnancy. These effects of LDN may prove to be effective in management patients with endometriosis.
Boyle PC et al., 2018·Front Med (Lausanne)·
Open Access
To determine the live birth rate for patients who chose to undergo treatment with Restorative Reproductive Medicine (RRM) after previous IVF (includes ICSI). To look at birth outcomes with RRM after IVF, particularly rates of twin and higher order pregnancies, premature birth, low birth weight, and potential cost savings achieved with RRM. Two outpatient clinics in Ireland providing advanced RRM treatment of infertility. All patients presenting between January 2004 and January 2010, with a history of infertility and previous IVF treatment were included if they proceeded beyond the initial consultation and began treatment. Main outcome is live birth per couple calculated using life table analysis. 403 patients met the study criteria, among which 74 had a subsequent live birth. These women had significant negative predictive characteristics for healthy live birth including: advanced reproductive age (average 37.2 years), an average of 5.8 years of infertility with 2.1 (range 1-9) previous IVF attempts, with only 5% having previously had a live birth from IVF. Despite these undesirable prognostic indicators, the overall RRM live birth rate was 32.1% (crude 18.4%). Women aged 35-38 had a live birth rate of 37.5% (crude 23.6%) and older women over 40 had a live birth rate of 27.4% (crude 16.0%). The average birth weight was 3374g (7lb 7oz) with 92% being born at 37+ weeks and no very low birth weight babies. There was only one twin pregnancy in the study population; the potential health care savings for avoidable multiple pregnancies in these patients was estimated at £205 672 (USD$284 915). Patients who have already tried IVF can achieve comparable live birth outcomes with RRM compared to another cycle of IVF. RRM has a low risk of twin or multiple births, and very good neonatal outcomes with a potential cost savings to the health care system.
Abdulla SH et al., 2018·Front Public Health·
Open Access
Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women.
Observational study.
Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four outcome measures were analyzed: short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level. A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG. Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.
Boyle PC et al., 2011·Biomedicina (Sveikatos Mokslai/Health Sciences)·
Infertility is usually a consequence of multiple chronic conditions rather than a single acute condition. We propose that it is erroneous to apply acute medical interventions to a condition that is chronic in nature.
Retrospective analysis of 3 case studies which demonstrate the multifactorial and chronic nature of infertility that were previously managed unsuccessfully with acute intervention using IVF (in Vitro Fertilisation) or ART (Assisted Reproductive Technology).
Demonstration of the multifactorial approach and 3 successful singleton live births using NPT (Natural Procreative Technology or NaProTechnology). Infertility can be treated successfully with a multifactorial approach which takes into account the chronic nature of infertility and targets treatment to manage multiple factors responsible for the condition. Infertility is not a diagnosis but is often the expression of several underlying ill health conditions which if diagnosed and treated correctly will result in restoration of normal reproductive function. Physicians ought to consider broader diagnostic possibilities in their evaluation of infertile couples. A multifactorial treatment strategy for the chronic condition of infertility may be more effective than the widespread acute strategy employed by ART. Further study is required to investigate this possibility in more detail. Future studies looking at NPT and ART outcomes must be cohort studies comparing populations with similar patient characteristics.
We evaluated outcomes in couples treated for infertility with natural procreative technology (NaProTechnology [corrected] NPT), a systematic medical approach for optimizing physiologic conditions for conception in vivo, from an Irish general practice. All couples receiving treatment from 2 NPT-trained family physicians between February 1998 and January 2002 were studied. The main outcome was live birth, and secondary outcomes included conceptions and multiple births. Crude proportions and adjusted life-table proportions were calculated per 100 couples. A total of 1239 couples had an initial consult for NPT, of which 1072 had been trying for at least a year to conceive and initiated treatment. The average female age was 35.8 years, the mean duration of attempting to conceive was 5.6 years, 24% had a prior birth, and 33% had previously attempted treatment with assisted reproductive technology (ART). All couples were taught to identify the fertile days of the menstrual cycle with the Creighton Model FertilityCare System, and most received additional medical treatment, including clomiphene (75%). In life-table analysis, the cumulative proportion of first live births for those completing up to 24 months of NPT treatment was 52.8 per 100 couples. The crude proportion was 25.5. Younger couples and couples without previous ART attempts had higher rates of live birth. Among live births, there were 4.6% twin births. NPT provided by trained general practitioners had live birth rates comparable to cohort studies of more invasive treatments, including ART. Further studies are warranted to compare NPT directly to other treatments.
Hilgers TW et al., 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
Patients who have undergone multiple failed IVF cycles and are counseled to abandon fertility treatment represent a significant NaProTECHNOLOGY cohort in whom undiagnosed correctable pathology — including subtle endometriosis, luteal insufficiency, or immunological factors — is subsequently identified and treated. Published data demonstrate clinically meaningful pregnancy rates in this population following NaProTECHNOLOGY evaluation and treatment, demonstrating that ART failure does not predict failure of restorative approaches.
Hilgers TW et al., 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
Family physicians are optimally positioned to introduce NaProTECHNOLOGY to patients presenting with infertility, irregular cycles, or recurrent pregnancy loss during routine primary care, enabling early evaluation and restorative treatment before referral to subspecialists. Familiarity with CrMS charting interpretation, basic hormone panels timed to identified cycle phases, and the range of treatable NaPro diagnoses allows the family physician to substantially expand reproductive care at the primary care level.