In Vitro Fertilization is Essential Healthcare for Patients With Rheumatic Disease

Abstract

Infertility presents a profound physical, emotional, and financial burden, particularly for rheumatology patients who often face substantial barriers to family building. The 2024 Alabama Supreme Court ruling in LePage v. Center for Reproductive Medicine equating embryo destruction with wrongful death introduced new legal uncertainties, sparking concerns about access to in vitro fertilization (IVF) and reproductive health services across the United States. Although Alabama's subsequent legislative action granted temporary protections for fertility providers, the broader implications of embryo personhood laws remain unresolved. For patients with rheumatic diseases, timely access to assisted reproductive technology (ART) is essential. However, barriers such as limited ART awareness, concerns about safety and success, social and religious stigma, and financial and legal restrictions disproportionately impact this population. The consequences of restrictive policies extend beyond females, affecting men and same‐sex couples who rely on IVF to expand their families. Infertility is a recognized medical condition, and restricting ART access is medically and ethically indefensible. As physicians, researchers, and advocates, we must actively oppose legal decisions and policies that limit ART availability, including insurance restrictions, discriminatory practices, and embryo personhood legislation. Protecting and expanding ART access is critical—not only for rheumatology patients but for the one in eight couples and one in four physicians affected by infertility. Ensuring equitable, evidence‐based reproductive care is imperative to safeguarding the right to family building for all.

Introduction

Infertility and navigating the challenges of assisted reproductive technology (ART) to become a parent are physically, emotionally, and financially demanding processes without the guarantee of a baby. On February 20, 2024, the Alabama Supreme Court ruled on a now landmark case, LePage v. Center for Reproductive Medicine, establishing that the destruction of an embryo created through in vitro fertilization (IVF) could be considered a wrongful death of a minor. This landmark decision assumes that an embryo has the same personhood as a living child. ¹ , ² Thus, those responsible for the embryo's destruction could be held liable based on state legislation from 1872. This ruling struck terror in the hearts of parents who care for one of the 80,000 children conceived annually through IVF in the United States, as well as owners of the hundreds of thousands of frozen embryos. ³ , ⁴ , ⁵ Providers of infertility care, fertility preservation, women's health, and urological care were outraged by the ruling, fully aware of the implications it held for their patients. ²

On March 6, 2024, after considerable external pressure, Alabama's governor signed a bill protecting fertility clinics, their employees, and patients. The law provides “civil and criminal immunity for death or damage to an embryo or any individual or entity when providing or receiving services related to IVF.¹” Although this offers some reassurance, it serves as a temporary fix rather than a long‐term solution, leaving unresolved the central question raised by the court's decision: Should an embryo created through IVF be treated as a child under Alabama law? In 2025, 19 states have presented 37 bills that include embryonic or fetal personhood language similar to Alabama's. ⁶ This highlights the importance of continued advocacy and physician involvement to protect patients’ right to build a family in the best way for them.

Rheumatology patients are once again deeply impacted by this repeat attack on reproductive health care, just as they were with the overturn of Roe v. Wade ⁷ through Dobbs v. Jackson Women's Health Organization ruling in June of 2022. ⁸ However, unlike the legal and medical consequences of Dobbs, which predominantly affects females, any restrictions on IVF will impact men as well, with downstream effects on the utilization of donor gametes, donor embryos, and surrogacy. The vast majority (90%) of those undergoing IVF in developed countries are heterosexual couples, with a small portion being same‐sex couples or those desiring to become a single parent. ⁹ However, male factor infertility (MFI) (eg, issues related to sperm creation, structure, or motility) accounts for upward of 50% of infertility and may be best addressed through IVF. ¹⁰ Additionally, men and people of color are more likely to have severe autoimmune rheumatic diseases such as lupus, leading to higher comorbidity burdens and greater use of teratogenic or infertility‐inducing medications, thereby placing these groups at disproportionate risk from IVF restrictions and making equitable access to ART particularly critical. ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵

Infertility

Before delving into the IVF needs of rheumatology patients, a review of key aspects of human reproductive biology is required. At birth, ovaries contain all the eggs a female will have in their lifetime. In contrast, in males, sperm production begins at puberty and continues for life. Once menstrual cycles have begun, a woman is fertile for approximately five days out of each typical 28‐day cycle. For a pregnancy to occur, a mature egg, released from an ovarian follicle, must travel through an unobstructed fallopian tube, where it is fertilized by a sperm with the necessary physical characteristics and motility. If successful, the fertilized egg transforms into a dividing cluster of cells as it travels to a hospitable uterus for implantation. Failure in transit can result in an ectopic pregnancy, a medical emergency. Given the complexity of this process, it is easy to comprehend why over 9 million Americans struggle with infertility. ¹⁶ , ¹⁷

Infertility was traditionally defined as the inability to conceive after 12 months of regular, unprotected intercourse for females under 35 years, or after six months for females 35 years and older. Recently, the American Society of Reproductive Medicine expanded this definition to include not only the previous criteria but also (1) the inability to achieve a successful pregnancy based on a patient's medical, sexual, and reproductive history, age, physical findings, diagnostic testing, or any combination of those factors and (2) the need for medical intervention, including, but not limited to the use of donor gametes or donor embryos in order to achieve a successful pregnancy either as an individual or with a partner. ¹⁸ This expanded definition of infertility will likely reveal an even higher prevalence than previously recognized, demonstrating an even greater need for equitable IVF access.

As medical professionals, we must recognize and emphasize that infertility is a medical diagnosis requiring safe, effective, and evidence‐based treatments delivered through open, patient‐centered care. These care decisions should rest in the hands of medical experts with extensive training in infertility and reproductive health and their patients, not politicians.

ART

The terminology and procedures associated with ART can be complex for individuals without specialized training or direct experience (Table 1). ART includes any assistance in conception, which may include oral pills like clomiphene or letrozole, or medication that can assist in egg release from the follicle, referred to as a “trigger shot.” Timed intercourse cycles involve having sexual intercourse when chances of ovulation are high, identified with increasing accuracy due to lab tests and follicular ultrasonography monitoring. Intrauterine insemination consists of placing semen directly into the uterus via a catheter when fertility is at its peak, often accompanied by medications mentioned earlier, and is similarly monitored. ¹⁹ None of the aforementioned procedures involves embryo creation outside the body. ¹⁹

Table 1.

ART procedures and terminology^*

Clomiphene and letrozole: Oral medications that stimulate ovarian follicle growth and can be used in ovulation‐timed intercourse or IUI.

IUI: Placement of sperm directly into a uterus using a catheter through the cervix at the appropriate time of one's menstrual cycle when most fertile.

IVF: Use of hormonal medications for ~ 8 to 14 days causes substantial ovarian follicular growth. When optimal, an oocyte (egg) retrieval is performed. During this typically sedated procedure, follicles are accessed from a vaginal approach, punctured with a needle, and the oocytes (eggs) surgically removed from the follicles with suction. They are combined with sperm and cultured for five to seven days to form an embryo. This whole process is often referred to as a “cycle.”

ICSI: Procedure used in IVF to inject a single sperm into a retrieved egg to assist in fertilization.

Embryo: Term used to describe the cluster of cells formed by fertilization, starting as a zygote, developing into a 16‐cell morula, and growing into an ~ 100‐cell blastocyst within five to seven days.

PGT: Testing of a small biopsy of cells from mature blastocysts to determine if euploid, aneuploid, or mosaic (PGT‐A). Additional testing can be done for known familial genetic mutations (PGT‐M) and gender.

FET: Direct placement of embryo(s) into prepared uterus with a catheter with hope for implantation and pregnancy.

Donor eggs or sperm or embryos: Eggs, sperm, or embryo that is not from those wishing to be parents. These can be from known donors, that is, family or friends or anonymous donors.

Oocyte cryopreservation “egg freezing”: Involves the same medications for IVF to cause substantial ovarian follicle growth as detailed. The oocytes (eggs) are surgically removed from the follicle with suction during an oocyte (egg) retrieval. Eggs are frozen, to be thawed and fertilized in the future.

Sperm cryopreservation: Freezing of sperm for future use. Sperm may be retrieved through ejaculation or surgical procedures.

Embryo banking: Creating embryo through IVF (with or without ICSI) to then be frozen to be transferred to a prepared uterus in the future.

Surrogacy: The use of a gestational carrier or “surrogate” to carry and delivery a child for intended parents. The embryo, created through IVF and transferred via FET, may be composed of any combination of sperm and egg from the intended parents, donor(s), or gestational carrier.

^*ART, Assisted reproductive technology; FET, frozen embryo transfer; ICSI, intracytoplasmic sperm injection; IUI, intrauterine insemination; IVF, in vitro fertilization; PGT, preimplantation genetic testing.

IVF is a type of ART comprised of three main components: (1) follicular growth and oocyte procurement, (2) embryo creation, and (3) embryo transfer. The process begins with a stimulation cycle where a combination of hormonal medications is given for one to two weeks to promote the growth of multiple ovarian oocyte‐containing follicles. Once follicles are matured, a hormone‐containing “trigger shot” is administered to mature the eggs and is followed by ultrasonography‐guided oocyte retrieval. During the oocyte retrieval, a large needle is inserted through the vaginal wall to access each ovarian follicle and collect the individual oocyte from the follicular fluid. An embryologist then examines the retrieved oocytes. The process stops here if the goal is egg freezing for fertility preservation. However, freezing embryos, as opposed to freezing eggs, yields a higher success rate regarding live births. ¹⁹

If proceeding with embryo creation, the embryologist selects mature oocytes and fertilizes them with semen in a test tube. Intracytoplasmic sperm injection (ICSI) is another fertilization technique that involves injecting a single sperm directly into an oocyte and is commonly used in cases of MFI. The fertilized eggs are incubated for five to seven days in hopes of growing into a mature blastocyst, colloquially termed an “embryo.” At this stage, the blastocyst can be (1) transferred into a prepared uterus, (2) frozen for future transfer, or (3) undergo preimplantation genetic testing (PGT). With PGT, a small biopsy of the embryo's outer cells is taken for testing before freezing. PGT can help identify embryos with genetic abnormalities that would make a successful pregnancy very unlikely, are incompatible with life, or significantly affect quality of life. PGT can determine sex chromosomes, facilitating embryo selection in cases of hereditary diseases or for family balancing. ¹⁹

Once pregnancy is desired, several steps are required to use a frozen embryo including the administration of medications to prepare the uterus for implantation, thawing the frozen embryo, and transferring the embryo into the uterus. As in unassisted conception, many variables must align for IVF success. Unfortunately, each stage, from gamete to embryo creation to embryo transfer, has significant attrition (Figure 1). Even with PGT, the success rate for a euploid embryo transfer is only about 60%. ¹⁹ , ²⁰ , ²¹ , ²²

Figure 1.

IVF cycle attrition. ASRM, American Society for Reproductive Medicine; IVF, in vitro fertilization; PGT, preimplantation genetic testing.

In cases where egg or sperm retrieval is not possible due to factors such as previous chemotherapy, surgery, age, or genetic conditions, donor oocytes, and/or sperm may be used. Donor embryos, typically frozen, can also facilitate childbearing goals. Additionally, when a uterus is absent or pregnancy is contraindicated, an embryo may be transferred to a gestational carrier (surrogate).

Rheumatic disease factors necessitating IVF access

There are multiple reasons why ART and IVF should be considered medically necessary interventions in patients with rheumatic disease (Table 2).

Table 2.

Factors contributing to the need for ART specific to patients with rheumatic disease^*

	Notes	Example
Factor
Rheumatic disease	Patients with rheumatic disease may need to delay family planning due to active disease, end organ damage related to their disease, and/or medications that are not compatible with pregnancy. If a female patient were to conceive when they are not optimized from a medical perspective, this can increase their risks for pregnancy complications including preterm delivery, pregnancy loss, and preeclampsia	Lupus nephritis, chronic kidney disease, interstitial lung disease, cardiomyopathy, pulmonary hypertension, vascular aneurysms, and heart failure
Gonadotoxic medications	Medications that impact ovarian reserve or spermatogenesis may be used to treat rheumatic disease and decrease fertility	Cyclophosphamide (egg and sperm) and sulfasalazine (sperm only)
Teratogenic medications	Medications that are not safe in pregnancy as they can cause miscarriages and/or congenital malformations, may be required to treat rheumatic disease and delay family planning	Methotrexate, mycophenolate containing medications, and cyclophosphamide
Concurrent fertility‐impacting diagnoses	Patients with rheumatic disease may be at increased risk for concurrent chronic conditions that impact fertility	Endometriosis, polycystic ovarian syndrome, diabetes, inflammatory bowel disease, celiac disease, asthma, and hypo or hyperthyroidism
Prior pregnancy complications or pregnancy contraindications	Patients may choose to pursue surrogacy due to prior pregnancy complications and/or complications of their rheumatic disease as listed above that may increase the risk of maternal and infant morbidity and mortality Preeclampsia, eclampsia, preterm delivery, need for Cesarean delivery, and HELLP syndrome
Advanced maternal age	Females with rheumatic diseases during their early reproductive years may be counseled or choose to defer pregnancy to later in life due to disease activity and/or teratogen use
Diminished ovarian reserve or premature ovarian insufficiency	Medications, systemic inflammation, and immune factors may decrease the number of follicles a woman has compared to her age norm
Physical impairment	Pain, fatigue, and a host of other complications of rheumatic disease can significantly impact libido and frequency of intercourse. Erectile dysfunction is significantly more common in those with rheumatic disease
Psychological well‐being	Patients with rheumatic disease experience lower self‐esteem and higher rates of depression and anxiety which can impact libido and frequency of intercourse
Amenorrhea or anovulatory cycles	Nonovulatory cycles may be due to active rheumatic disease, associated comorbidities such as renal disease, or medication side effects
Low testosterone	Low testosterone is more common in men with rheumatic disease, which can affect spermatogenesis
Autoantibodies	Positive antiphospholipid and thyroid peroxidase antibodies are associated with decreased fertility
Medications
CYC	Interferes with spermatogenesis and oogenesis and can cause irreversible infertility or prolonged oligospermia especially at cumulative doses ≥7.5 g/m2. Older age is associated with an increased impact of CYC on infertility
NSAIDs and aspirin	Reversibly negatively affects sperm motility, viability, count, and DNA integrity. Cyclooxygenase inhibition blocks prostaglandin synthesis which prevents oocyte release, leading to luteinized unruptured follicle syndrome. High‐dose aspirin >2.6 g/day can decrease spermatogenesis
Glucocorticoids	Contributes to obesity and metabolic syndrome in males and females by influencing the hypothalamic‐pituitary‐gonadal axis. Contributes to anovulatory cycles and menstrual abnormalities by reducing levels of luteinizing hormone and follicle stimulating hormone. Prolonged or high dose corticosteroid use can lower testosterone levels but does not seem to impact fertility directly
Sulfasalazine	Reduced sperm density and motility and a reversible azoospermia can be seen at doses >2 g/day. Routine discontinuation before conception is not necessary; however, if conception is delayed, sulfasalazine should be held for three months and semen analysis performed

^*ART, Assisted reproductive technology; CYC, cyclophosphamide; HELLP, hemolysis, elevated liver enzymes, and low platelets; NSAID, nonsteroidal anti‐inflammatory drug.

Impact of rheumatic diagnosis on timing of conception

Autoimmune diseases and their treatments can influence patients’ decisions about the timing of family planning. ¹³ , ¹⁴ Pregnancies in patients with autoimmune diseases carry higher risks of complications and benefit greatly from planning during periods of well‐controlled disease and use of pregnancy‐compatible medications. ²³ Rheumatology patients may need to delay reproductive goals due to (1) high disease activity, (2) pregnancy‐incompatible medications, (3) lack of a co‐parent, or (4) personal and financial burdens related to complex medical conditions. ²⁴ For example, a 25‐year‐old with systemic lupus erythematosus (SLE) and lupus nephritis typically requires at least two years of mycophenolate mofetil, a teratogenic medication. After reaching remission, a three to six‐month period is recommended to transition to pregnancy‐safe immunosuppressives and confirm disease quiescence. Even a single uncomplicated lupus nephritis flare can delay a safe pregnancy by three years. ²⁵

As females approach age 35, egg quality declines, increasing infertility risk and the need for ART. ²⁶ For rheumatology patients needing to delay pregnancy, access to ART for fertility preservation provides an essential opportunity to prioritize health without sacrificing future family plans.

For anatomically male patients, the key consideration when timing pregnancy is to avoid conception during cyclophosphamide (CYC) treatment or within three months after the last dose due to its spermatotoxic effects. ²⁵

Impact of rheumatic diagnosis on fertility

Infertility in patients with autoimmune diseases is multifactorial. Teratogen use and conception delays, often leading to advanced maternal age, increase the risk of infertility and miscarriage. ²⁷ Additionally, ovarian insufficiency, spermatotoxicity, and azoospermia from certain medications used to treat rheumatic disease contribute to infertility. These examples demonstrate the indirect impact of autoimmune disease on fertility through treatment‐related therapies and delayed family planning.

Rheumatology patients may also experience infertility as a direct impact of their autoimmune disease. Diminished ovarian reserve has been demonstrated in females who have SLE, RA, and/or antiphospholipid antibodies independent of exposure to ovarian‐toxic immunosuppression. ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² Those with childhood‐onset SLE, juvenile dermatomyositis, or juvenile idiopathic arthritis have also been found to have laboratory evidence of lower ovarian reserve compared to their peers. ³³ It is theorized that dysregulated lymphocyte subsets and the presence of autoantibodies may affect estrogen and progesterone levels, potentially impacting ovarian function and fertility. ²⁹ Higher levels of inflammation and associated disease activity are associated with irregular menstrual cycles and prolonged amenorrhea, which can contribute to fertility issues. ³⁴ Chronic kidney disease (CKD) is common in a number of rheumatic diseases and can independently impact fertility. ³⁵ Premature ovarian insufficiency (POI) has increased incidence with rheumatic and other autoimmune diseases. ³⁶ Because autoimmune diagnoses often cluster, patients with rheumatic disease may have other diagnoses that negatively impact fertility, such as autoimmune thyroid disease, celiac disease, and type 1 diabetes. ³⁷ Autoimmune diseases can continue to impact fertility beyond ovarian reserve, with studies demonstrating significantly decreased rates of embryo implantation and good‐quality blastocyst formation in females with SLE who pursue IVF. ³⁸

Patients with rheumatic diseases may experience sexual dysfunction. Sexual dysfunction is a comprehensive term that describes decreased interest in sex, inability to achieve orgasm, and dyspareunia. A meta‐analysis found that 63% of females with rheumatic diseases experience sexual dysfunction, with Sjogren syndrome having the highest prevalence at 74%, similar to rates seen in conditions such as renal failure and cervical cancer. ³⁹ Sexual dysfunction is well characterized in male patients with autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and Addisons disease. ⁴⁰ , ⁴¹ , ⁴² This highlights the emotional and psychologic toll chronic diseases can have on patients and their personal and reproductive health goals. ART offers a path to achieving these goals while navigating the complexities of autoimmune diseases.

Gonadotoxic medication utilization

CYC, a chemotherapy agent typically reserved for critically ill rheumatology patients, has known gonadotoxic effects on both sperm and eggs. In females, CYC exposure can accelerate time to menopause by reducing ovarian reserve, as reflected by decreased anti‐Müllerian hormone and antral follicle count. The gonadotoxicity of CYC is also dose‐dependent. A cumulative lifetime dose of >7.5 g/m² is well‐established to impact fertility across sexes. ⁴³ , ⁴⁴ , ⁴⁵ Although contemporary CYC dosing aims to minimize cumulative exposure, patients with chronic rheumatic diseases often experience episodic flares, making multiple CYC courses over their reproductive lifespan not uncommon. Multiple courses of CYC can easily exceed the 7.5 g/m² threshold, particularly if diagnosed in childhood or as a young adult. Notably, men and people of color are more likely to present with aggressive or organ‐threatening autoimmune rheumatic diseases that necessitate CYC use, further concentrating gonadotoxic exposure in populations already facing substantial health and fertility inequities. ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ⁴⁶ , ⁴⁷ SLE and antineutrophil cytoplasmic antibody‐associated vasculitis are the two most common diagnoses treated by CYC, and both conditions tend to be more severe in children. ⁴³ , ⁴⁴ , ⁴⁵

The American College of Rheumatology (ACR) and other medical organizations recommend offering fertility preservation in males and females with its use. ²⁵ Although cryopreservation is preferred due to subsequent success rates for future conception, many rheumatology patients are too critically ill or lack the time and financial means to pursue it. Additionally, chronic glucocorticoid use, which is common in rheumatology, is also thought to impact fertility. ⁴⁸ , ⁴⁹

Concurrent fertility‐impacting diagnoses

Some rheumatology patients, such as a 30‐year‐old with newly diagnosed rheumatoid arthritis well‐controlled on pregnancy‐compatible medications, may not face the infertility risks mentioned earlier. However, they may still encounter conception challenges and require access to IVF for other reasons.

MFI

Approximately 50% of infertility cases can be attributed to male factors such as abnormal sperm production or physical characteristics, obstruction or inability to ejaculate, and low or absent sperm counts. ⁵⁰ Retrieved sperm used in ICSI after egg retrieval can overcome many of these barriers. For azoospermia or absent testicles, donor sperm can be used.

Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS), characterized by multiple ovarian cysts, is a hormonal imbalance resulting from excess androgen production. This leads to irregular ovulation and oligo‐ or amenorrhea, along with clinical signs of androgen excess like hirsutism, acne, and metabolic abnormalities. One in 10 females worldwide have PCOS, and 50% of these females experience infertility. ⁵¹ The incidence of PCOS is increased in patients with rheumatic disease. ⁵² , ⁵³

Endometriosis

Endometriosis is a chronic condition in which endometrial tissue implants outside the uterine cavity, causing pain, scarring, and infertility. It accounts for about 50% of infertility cases, often diagnosed only when they are unable to conceive. ⁵⁴ The incidence of endometriosis is comparable to that of PCOS, with both conditions typically starting in puberty. ⁵⁵ The prevalence of endometriosis is increased in those with autoimmune diseases. Conversely, a diagnosis of endometriosis is associated with a higher risk of developing an autoimmune condition, highlighting gaps in the understanding of this common condition. ⁵³ , ⁵⁶ , ⁵⁷ Endometriosis should be considered in rheumatology patients with dysmenorrhea, menorrhagia, chronic abdominal pain, or rectal pain during menstruation, even if not trying to conceive, due to its potential long‐term fertility impact.

Tubal issues

Ectopic pregnancies, which account for 1% to 2% of all pregnancies, occur in the fallopian tube 95% of the time. ⁵⁸ Tubal rupture occurs in 15% of ectopic pregnancies, often requiring surgical removal of the tube. ⁵⁹ Approximately 5% of females in the United States have pelvic inflammatory disease (PID), ⁶⁰ a condition caused by microorganisms ascending from the vagina or cervix to the uterus and fallopian tubes. It remains unclear whether immunosuppression increases the risk of PID, but it may mask inflammatory symptoms, delaying diagnosis and leading to more severe infections and damage. PID can cause infertility by inducing fallopian tube inflammation, scarring, and obstruction, which can result in ectopic pregnancies and impaired sperm access to oocytes. PID may also lead to endometritis or fallopian tube loss from tubo‐ovarian abscesses. Additionally, genital infections can contribute to male infertility. ⁶¹

Associated autoimmune diseases

Many patients with rheumatic disease have multiple autoimmune conditions. Autoimmune disorders not typically managed by rheumatologists—such as psoriasis, ⁶² , ⁶³ inflammatory bowel disease, ⁶⁴ celiac disease, ⁶⁵ asthma, ⁶⁶ autoimmune thyroid disease, ⁶⁷ and type I diabetes ⁶⁸ , ⁶⁹ —are also associated with infertility in both females and males. Endocrine dysfunction affecting the thyroid, pituitary, hypothalamus, or adrenal glands can contribute to infertility but may be managed through hormonal regulation during IVF.

Other factors

Uterine factors such as fibroids, adenomyosis, congenital malformations, or uterine absence may necessitate IVF. Rheumatology patients, including single parents by choice and same‐sex couples, may not be “infertile” but still require ART to achieve their family‐building goals. Transgender patients have multiple IVF options for family building, including fertility preservation before hormone therapy or surgery, using donor or partner gametes, embryo transfer to their uterus, or reciprocal or reverse IVF.

Need for surrogacy

In rheumatology, surrogacy may be necessary for various reasons. It involves a gestational carrier, or “surrogate,” who carries a pregnancy but is typically not biologically related to the baby. The embryo is created through IVF and then transferred to the carrier. The necessity of teratogenic medications to control rheumatic diseases may lead patients to consider surrogacy. Methotrexate, mycophenolate, CYC, and leflunomide are commonly used in rheumatology to treat various conditions, including systemic vasculitis, myositis, inflammatory arthritis, and lupus. Mycophenolate and CYC are often prescribed for severe or life‐threatening cases (eg, myocarditis, central nervous system vasculitis, nephritis, cerebritis, interstitial lung disease [ILD]). These medications are well‐established teratogens known to cause pregnancy loss and birth defects. For example, mycophenolate has a 45% risk of early pregnancy loss and a 25% chance of fetal malformation. ⁷⁰ , ⁷¹

For some patients, discontinuing pregnancy‐incompatible medications is not feasible. Even under medical supervision, stopping these treatments can trigger disease flares, cause irreversible organ damage, or, in severe cases, be life‐threatening. Although pregnancy‐compatible alternatives like azathioprine and tacrolimus exist, they may be ineffective or poorly tolerated. For example, a female patient with difficult‐to‐control neuropsychiatric lupus or lupus nephritis, well‐controlled on mycophenolate, may choose to pursue motherhood through IVF and surrogacy instead of switching to pregnancy‐compatible medications due to a justified fear of disease flare, especially if previous attempts to make this transition have failed.

Pre‐existing end‐organ impairment, regardless of the specific rheumatic disease, is another reason to consider surrogacy. For patients with pulmonary arterial hypertension (PAH), pulmonary hypertension, cardiomyopathy, advanced CKD or end‐stage renal disease, ILD, severe valvular heart disease, heart failure, or aorta abnormalities, the prospect of pregnancy entails a markedly elevated risk of morbidity and mortality for both the mother and the pregnancy. PAH is associated with a 20% risk of maternal mortality, even with aggressive treatment. ⁷² Subspecialty‐specific and maternal health organizations recommend against pregnancy in patients with the aforementioned conditions. ²⁵

Compounding the complexity of managing rheumatologic conditions during pregnancy are the heightened risks of severe pregnancy complications inherent to many autoimmune diseases—preeclampsia; eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and hemorrhage. In conditions like SLE and Anti‐phospholipid Antibody Syndrome (APS), rates of flare and new‐onset disease are increased during times of hormonal fluctuation. Those with APS or who are antiphospholipid antibody positive are strongly advised to abstain from estrogen‐containing products. Pregnancy itself induces a prothrombotic state marked by hormonal fluctuations and extremely elevated estrogen levels. Although IVF typically involves inducing significant hormonal fluctuations and high serum estrogen (if the egg comes from the intended parent), the process is controlled, of limited duration (~ 2 weeks), and is more predictable, compared to pregnancy. In some cases, the hormonal fluctuations inherent to pregnancy pose an intolerable risk, necessitating vigilant risk assessment and personalized management strategies, which could include IVF and surrogacy. ²⁵

Patients may opt to use IVF and surrogacy with the desire to limit risk to their offspring. Congenital heart block (CHB) is an antibody‐mediated inflammation in the fetal cardiac conduction system caused by the transplacental passage of maternal circulating anti‐SSA/Ro antibodies. Females with SSA/Ro autoantibodies carry an estimated 2% to 7% risk of giving birth to a child with CHB, with a 10% to 20% chance of recurrence in subsequent pregnancies. ⁷³ CHB can cause fetal hydrops, resulting in fetal death. ⁷⁴ Infants born to females with high titers of the Ro52 antibody are at the greatest risk for CHB. Using a gestational carrier negates the risk of CHB. ⁷⁵

Finally, surrogacy is the only option for men with rheumatic diseases—whether partnered with another male or seeking to become single parents—to have a biologically related child. This can be achieved through IVF, where the surrogate carries an embryo created from the desired parent's sperm. Sadly, LGBTQIA+ couples and individuals encounter significant bias within the ART sector, with some clinics and agencies refusing to provide care. ⁷⁶ , ⁷⁷

Even if IVF as a medical treatment is recommended and accessible, barriers to ART are plentiful for rheumatology patients. A single IVF cycle in the United States costs between $15,000 to 30,000. ⁷⁸ , ⁷⁹ Only a dozen states have a fertility mandate that requires private insurance to cover some aspect of infertility treatment. In addition to procedure costs, frozen gametes and embryos have annual storage fees of approximately $1,000. Rare is the insurance plan that covers ART for fertility preservation. ⁸⁰ , ⁸¹ , ⁸² , ⁸³ Medicaid and Medicare do not cover fertility evaluations or treatments, placing rheumatic patients with government‐based insurance at a reproductive disadvantage. ⁸⁴ Although oncology patients receiving gonadotoxic chemotherapy, radiation, and/or undergoing procedures resulting in surgical sterilization may have insurance coverage for fertility preservation, rheumatic diagnoses are not included. Additionally, a number of grant and assistance programs are available for patients with cancer, but are nonexistent in rheumatology. ⁸⁵ , ⁸⁶ , ⁸⁷

Restorative reproductive medicine

Of recent, new approaches like restorative reproductive medicine (RRM) have gained attention, often reframing infertility through a moral rather than medical lens. RRM takes a “natural” approach to infertility, focusing on lifestyle changes, cycle tracking, and treating conditions like endometriosis, while rejecting IVF on moral grounds tied to the antiabortion “personhood” movement. ⁸¹ , ⁸⁵ This movement shares many similarities with natural procreative technology (“NaPro”), a pro‐life women's health medical technology in line with the Catholic church's teachings. ⁸² Although RRM presents itself as compassionate and holistic, in practice, it often places the burden of infertility on women and overlooks male‐factor infertility. It also excludes many families, such as LGBTQ+ individuals and single parents who rely on ART to have children. For many, these restrictions can mean delayed treatment, higher costs, and greater emotional burden. ⁸³ , ⁸⁵ None of this is new, though. People have pushed back against IVF for years, mostly using religious or political arguments that paint laboratory‐assisted conception as some unnatural “creation of life.” RRM and NaPro continue this narrative by promoting unproven alternatives while dismissing decades of evidence showing how transformative IVF can be for conditions like blocked fallopian tubes or severe male infertility. ⁸⁴ When access to proven, evidence‐based care is limited by ideology rather than science, patients are the ones who suffer. RRM's growing influence highlights why reproductive policies must center compassion, evidence, and patient choice, ensuring that every person or couple has the chance to build a family in the way that's right for them. ⁸¹ , ⁸⁵

Conclusions

Rheumatology patients face significant challenges in achieving their family‐building goals. Their unique needs—ranging from fertility preservation and pregnancy timing to IVF utilization—demand a health care system that supports, rather than hinders, access to these essential services. Barriers such as limited awareness of ART, concerns about safety and success, social and religious stigmas, and financial and logistical constraints must be addressed to ensure equitable care. ⁸⁸

Infertility is a recognized medical diagnosis; obstructing anyone's access to its treatment is unacceptable. As physicians, researchers, and allied health professionals, we have a responsibility to oppose policies and legal rulings that limit or complicate access to IVF and ART. This includes insurance restrictions, discriminatory policies based on age, race, ethnicity, gender, or sexual orientation, and legislation granting legal personhood to embryos.

Advocating for guaranteed and expanded ART access is critical—not just for rheumatology patients but for all individuals facing infertility. With one in eight couples and one in four physicians affected, ⁸⁹ , ⁹⁰ protecting and broadening IVF access nationwide is imperative to ensuring that everyone can safely pursue their family building goals.

AUTHOR CONTRIBUTIONS

All authors contributed to at least one of the following manuscript preparation roles: conceptualization AND/OR methodology, software, investigation, formal analysis, data curation, visualization, and validation AND drafting or reviewing/editing the final draft. As corresponding author, Dr Edens confirms that all authors have provided the final approval of the version to be published and takes responsibility for the affirmations regarding article submission (eg, not under consideration by another journal), the integrity of the data presented, and the statements regarding compliance with institutional review board/Declaration of Helsinki requirements.

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