Publication
Research Article
Background: Comprehensive management of multiple sclerosis (MS) requires a multispecialty approach. Routine health care must not be neglected but maintained in consideration of the complexity and variety of consequences of the disease process. This study assesses the confidence of obstetric and gynecological providers (OBGYNs) when caring for people with MS.
Methods: OBGYNs, including doctors, physician assistants, and advanced nurse practitioners within Hackensack Meridian Health, completed a survey assessing their comfort level with and knowledge of how to care for patients with MS.
Results: The survey was completed by 29.2% of eligible providers. Most reported that people with MS tend to have sexual and bladder dysfunction; contraceptive management does not change; and pregnancy influences the disease process. They were split regarding the risk of infertility in and the impact of menopause on people with MS. There were no statistically significant differences in the recommendations of providers of varying levels of experience on any topic.
Conclusions: Provider recommendations, regardless of their level of experience, highlight the gaps in the available literature, indicating a need for further research to guide clinical management. Dedicated education on existing guidelines for OBGYN care for people with MS is necessary to improve provider comfort.
From the Departments of Obstetrics and Gynecology (KLB, AFO) and the Department of Neurology (KP), Hackensack University Medical Center, Hackensack Meridian Health Network, Hackensack, NJ. Correspondence: Krupa Pandey, MD, Director of the Clinical Research Division of the Neurosciences Institute, Director of MS Comprehensive Care Center, Neurosciences Institute at Hackensack University Medical Center, 360 Essex St, Suite 303, Hackensack, NJ 07601; email: Krupa.pandey@hmhn.org.
Multiple sclerosis (MS) is a chronic demyelinating disease affecting approximately 1 million people in the United States, with the highest incidence in the northeast of the country.1 Women of childbearing age (median age at diagnosis, 20-50 years) are mostly affected at a ratio of 3:1 compared to men.1 Therefore, the impact on decisions regarding medication and reproductive health can be significant for people with MS. Additionally, as the treatment armamentarium expands and efficacy improves, the number of people with MS who will need postmenopausal care will also rise.
Topics such as contraception; family planning; pregnancy; menopause; and pelvic, sexual, and bladder disorders are complex and require a thorough understanding of the most current literature, including the incorporation of existing guidelines. Literature is available regarding the impact of MS on fertility treatments,2 conception,3 pregnancy,4 and the postpartum period,5 along with existing Centers for Disease Control guidelines for contraception use by people with MS.6 However, although neurologists may be aware of this body of information,7,8 it is unclear whether the obstetric and gynecologic provider (OBGYN) community is informed.
As management strategies of reproductive health issues differ among neurologists,8 there is likely a need for improvement in the field of OBGYN for the treatment of individuals with MS. We hypothesized that our hospital network, despite it being in a location with a higher incidence of MS, was not unique to these gaps in care, and we sought to understand providers’ specific discomforts in treating patients with MS. This study assesses OBGYN care providers’ confidence in treating patients with MS through a survey of providers within a single hospital network.
Study Population
All OBGYNs (approximately 120 medical doctors [MDs], osteopathic doctors [DOs], physician assistants [PAs], and advanced practice nurses [APNs] within Hackensack Meridian Health, a single health network comprising 18 hospitals across the state of New Jersey, were contacted by email to complete a REDCap survey. The survey content was generated via a collaboration between a maternal-fetal medicine physician and a neurologist specializing in MS care. It assessed the OBGYNs’ knowledge of MS and the providers’ comfort level with caring for these patients (Table S1, available as a PDF at the bottom of the online article), including providers’ standards of care for MS and routine care. Comfort level was assessed at the beginning and reassessed at the end of the survey to determine whether completion of the survey changed participants’ perspectives. Responses were collected over a period of 12 weeks and were anonymous. With a response rate of 29.2%, 35 OBGYNs participated. The margin of error is 14.0% with a 95% CI.
Statistical Analysis
We used a 2-way analysis of variance (with Tukey test for post hoc pairwise differences) for multiple independent group comparisons. A 2-tailed P value less than .05 was regarded as statistically significant. All statistical analyses were performed using Prism, version 9, for Windows (GraphPad Software Inc).
Study Approval
The Hackensack University Medical Center Institutional Review Board (IRB) approved all procedures (Hackensack, NJ; IRB Pro2022-0237). A waiver of signed consent was obtained, as there was no more than minimal risk to participants and no identifiable information collected. No personal health information was collected, so no waiver of Health Insurance Portability and Accountability Act privacy authorization was required.
Study Population
Of the 35 respondents, 85.7% were physicians, 5.7% were PAs, and 8.6% were APNs (Table). The majority of respondents were general obstetricians and gynecologists (n = 27, 77.1%), but also included were maternal-fetal medicine specialists (n = 6, 17.1%) and reproductive endocrinology and infertility specialists (n = 2, 5.7%). Respondents fell into the end ranges of practice in the field, 0 to less than 5 years (n = 11, 31.4% and greater than 20 years (n = 12, 34.3%). Practice settings included inpatient (n = 25, 71.4%), outpatient (n = 21, 60%), academic hospital (n = 24, 68.6%), community hospital (n = 4, 11.4%), multispecialty group (n = 1, 2.9%), single-specialty group (n = 11, 31.4%), and solo private practice (n = 2, 5.7%). Most respondents practiced in small or large cities, with none from rural areas.
Table. Characteristics of Participant Providers
The majority of respondents reported having treated a patient with MS (n = 25, 71.4%), and 40% reported having treated a patient with MS within the past 6 months to 1 year. Self-reported confidence was assessed, with 17 (48.6%) reporting poor confidence, 16 (45.7%) somewhat confident, and 2 (5.7%) very confident. After completion of the survey, 1 respondent remained very confident (2.9%), 14 (40%) were somewhat confident, and 20 (57.1%) reported poor confidence in their knowledge of managing MS. There was no difference in provider confidence based on years of experience (Figure 1). There were also no statistically significant differences in recommendations among providers of varying levels of expertise on all topics (Figure 2): contraception, P < .5620; sexual dysfunction, P < .1200; bladder dysfunction, P < .1991; fertility-related concerns, P < .6991; pregnancy, P < .7473; and menopause, P < .7668.
Figure 1. Confidence Levels Before and After the Survey by Years of Experience
Figure 2. Comparison of Provider Recommendations Based on Level of Experience
Contraception
Participants were assessed regarding their contraception recommendations when counseling people with MS, and 28.6% (n = 10) endorsed a change in recommendation when compared with patients without MS. Some of the open responses regarding the reason for this change included increased risk for clotting and avoidance of combined oral contraceptives with prolonged patient immobility. Five participants who denied adjusting recommendations were aware of the guidelines that exist for contraceptive use in people with MS. Sexually transmitted infection (STI) screening in patients with MS after they initiated immunotherapy was endorsed by 15 (42.9%) of respondents.
Sexual and Bladder Dysfunction
Although 82.9% (n = 29) of participants reported that people with MS will have sexual dysfunction and 82.3% recommended yearly screening (biannual, 5.8% and every 2-3 years, 11.7%), only 57.1% (n = 20) reported screening for it. Bladder dysfunction was endorsed by 91.4% (n = 32) of providers, and 62.9% (n = 22) reported screening for bladder dysfunction in patients with MS. Yearly screening was recommended by 90% of participants, and 10% of respondents recommended screening every 2 to 3 years.
Family Planning
Participants were split on whether to counsel patients on conception: 51.5% supported counseling and 48.5% did not. For infertility, 41.2% (n = 14) of the health care providers reported that patients with MS experience an increased risk, and 20% (n = 7) have managed a patient with MS with infertility. There was a notable low response rate to the prompt, “Do you change your management of infertility for patients with MS?” with 5 of 7 participants (71.4%) saying no. As for infertility screening, 32.4% of respondents (n = 11) do screen, with the majority screening yearly (80%). Before conception, patients were not advised to discontinue their disease-modifying therapies (DMTs) by 84.3% (n = 27) of those responding to the survey.
Pregnancy
Approximately half of the providers had treated a patient with MS during pregnancy (n = 16, 47.1%), and 65.7% (n = 23) of participants were aware of the risks associated with pregnancy for individuals with MS. Reported risks included predominantly increased risk of disease relapse, progression, and neurologic impact. Additional risks included preterm labor and birth, pregnancy loss, fetal growth restriction, preeclampsia, infection, deep vein thrombosis, and anesthesia complications. The majority believed that pregnancy can affect MS disease severity (n = 27, 77.1%); 62.5% of the participants stated that it worsens the disease. As for DMTs, 45.7% (n = 16) of participants were aware that medication plans should change during pregnancy.
Menopause
Eighteen participants (54.5%) stated that menopause was not associated with changing symptoms. No additional screenings were recommended by 78.8% of participants. Those who did recommend additional screenings advised monitoring follicle-stimulating hormone and estrogen levels and screening for osteoporosis.
MS affects substantially more female than male patients, often with an onset during their reproductive years.1 Contraception, sexual and bladder dysfunction, conception, pregnancy, and menopause are important issues that need to be considered by providers treating patients with reproductive capacity. In a survey of neurologists, many deferred their advice regarding reproductive care for their MS patients to OBGYNs,9 but gaps in knowledge could not be identified. This study is the first to assess the OBGYN clinical care gaps in the treatment of patients with MS. The majority of OBGYNs participating in this survey reported treating patients with MS, but most reported poor confidence in treating those patients. We therefore sought to review current guidelines in response to these providers’ practice of reproductive health issues.
Contraception
Family planning is an individually tailored choice that may be influenced by disease activity, treatment response, and resources for supporting parenthood in patients with MS. The diagnosis of a chronic neurologic illness alone may influence an individual’s intention to conceive. A comprehensive discussion about contraceptive options—including their safety, availability, and effectiveness—should be conducted with each patient. Although the body of evidence assessing health outcomes for patients with MS using contraceptives is limited, the Centers for Disease Control has provided guidelines for providers.6 There are no restrictions for contraceptives for patients with MS without prolonged immobility, although depot medroxyprogesterone acetate (DMPA) is recommended with careful follow-up. Combined hormonal contraceptives are not advised in patients with prolonged immobility unless no other contraceptive methods are available.
In this study, few respondents reported changing their recommendations for contraception for patients with MS. Of those that endorsed change, some identified the increased risk of coagulability due to immobility, restricting recommendations of combined hormonal contraceptives. Although the inferred concerns about venous thromboembolism were identified for DMPA use as well, providers did not identify concerns about bone health with the use of DMPA. Patients with MS might have compromised bone health from disease-related disability, immobility, or use of corticosteroids, and the use of DMPA has been associated with small changes in bone mineral density. Current recommendations include close follow-up for those who elect to use DMPA.6 Additional recommendations not noted by our participants are that many symptomatic therapies used for patients with MS, including modafinil and many anticonvulsants, may decrease the efficacy of oral contraceptives.6 Additional logistic issues may include difficulty swallowing pills or impaired fine-motor control in the hands, which is needed for placing vaginal rings and barrier methods, although there are no warnings about using these contraceptives.
There is no known association between the use of DMTs for MS and an increased risk of STIs. Not surprisingly, no guidelines exist for patients with MS and STI screening. However, patients on DMTs may be at increased risk of infection due to their immunosuppressive nature.10 This lack of evidence-based data likely contributes to the split in provider recommendations for screening patients with MS for STIs.
Sexual and Bladder Dysfunction
Sexual dysfunction in MS is understood to be the result of lesions in the neural pathways that are involved in physiologic function in combination with anatomic, biological, medical, and psychological factors. Approximately 40% to 80% of women with MS experience sexual problems, including reduced libido, anorgasmia, reduced tactile sensations in the thigh and genital regions, and dyspareunia secondary to vaginal dryness.11 Although providers are aware, screening is not common, and stigma around discussing sexual health may prevent patients from bringing this concern to their providers. As many treatment modalities exist, screening with tools like the Multiple Sclerosis Intimacy and Sexuality Questionnaire-15 (MSISQ-15) is encouraged to improve patient quality of life and physical relationships that rely on tactile/sensory stimulation to achieve orgasms. This study did not assess the management of sexual dysfunction, but pharmacologic, psychotherapy, devices, and mindfulness techniques can improve the negative impact sexual dysfunction has on patients’ quality of life. After a recommended first-line combination treatment of physical exercises, including yoga, pelvic floor exercises, and aqua therapy, patients may have improved restoration in sexual dysfunction with an onabotulinumtoxinA intradetrusor injection.12 Current studies supporting these recommendations are limited by small sample sizes, with the exclusion of menopausal patients, and a lack of information about psychological comorbidities and their associated medications.
Similar to sexual dysfunction, complex mechanisms are thought to impact bladder dysfunction in patients with MS, as its presence does not always correlate well with MRI lesions.13 Between 32% and 97% of patients with MS experience bladder symptoms, with urinary urgency being the most common.13 Neurogenic bladder is often associated with sexual dysfunction, but it can also lead to severe complications associated with bladder dysfunction, such as urosepsis. Treatment not only improves patient comfort but also prevents significant causes of morbidity. Counseling and bladder diaries may help classify the individual’s specific issues. Pelvic floor physiotherapy, medications, and procedures such as percutaneous tibial nerve stimulation are effective treatments for bladder dysfunction in patients with MS, indicating that screening should be further encouraged by OBGYNs.14
Family Planning
Although OBGYNs were divided in their concern about the disease process of MS causing infertility, there is currently no evidence that MS significantly impairs fertility.15 Evidence shows that inflammatory status may damage ovarian reserve, but there is a paucity of data regarding the true impact of MS disease progression on ovarian damage.16 A recent systematic review found that the anti-Müllerian hormone, the ovarian reserve marker, was not different in patients with MS compared with controls, but did find alterations in antral follicle count, estradiol, and luteinizing hormone levels.15 These data were confounded by a lack of consistency among DMT regimens for enrolled patients, which may have affected ovarian dysfunction. While increased menstrual irregularities have been previously noted after MS onset, acknowledging a possible relationship between disease and endocrine pattern changes, the true impact of these hormonal changes on ovarian reserve in patients with MS is unclear. Studies on fertility for people with MS have not taken into consideration the impact of an MS diagnosis on family planning.17
Although the relationship between MS and fertility remains unclear, patients may consider fertility treatments such as in vitro fertilization (IVF). Thus, providers should be aware of any impact that IVF treatment might have on the disease process of MS. Fertility treatment itself does not apparently affect relapse rates during this period of pronounced hormonal fluctuations and stressors, and DMT use during fertility treatments may reduce the risk of relapse.18
Providers were also divided on counseling patients with MS about conception. Each patient with MS should be considered individually to determine an optimal time for conception, taking into consideration disease activity, response to treatment, and parenthood resources or support. Although the overwhelming majority of providers recommended continuing DMTs prior to conception, the National MS Society does recommend a washout period for some treatments prior to attempting conception due to known risks to the fetus.19 Data demonstrate that interferon-ß and glatiramer acetate are safe to be taken up until conception and during pregnancy, but no DMTs are currently approved by the US Food and Drug Administration for use during pregnancy.20-22 Given the advent of newer medications with shorter half-lives and higher efficacy, allowing for treatment immediately before planned conception, washouts should be determined on an individual basis with providers.
Pregnancy
After an MS diagnosis, 1 out of every 3 patients with reproductive capacity becomes pregnant.23 It is therefore unsurprising that approximately half of the survey respondents endorsed treating a patient with MS through pregnancy, and most respondents were in agreement that pregnancy affects MS disease severity. In 1998, the Pregnancy in Multiple Sclerosis (PRIMS) study was the first to study 269 pregnancies of patients with MS.24 PRIMS data showed that pregnant patients with MS experienced reduced antenatal relapse, especially during the third trimester, but a significant increase in postpartum relapse with increased risk 3 months after delivery. Even in women with postpartum exacerbations, however, there is currently no evidence that pregnancy affects MS progression.25 Risk reduction for relapse in the postpartum period may include early follow-up with initiation of DMT therapy and exclusive breastmilk feeding in the first 6 months.26 Breastfeeding provides health, psychological, and societal benefits to both mother and newborn. Some DMTs have evidence of minimal transfer into breas tmilk (ie, interferon-ß and glatiramer acetate), which could support decisions to both breastfeed and resume DMT post partum on a case-by-case basis.26 Our study did not address concerns for breastmilk feeding.
There is no evidence that MS leads to any antepartum or peripartum complications.4 Despite some respondents having concerns about stillbirth or miscarriage, pregnancy loss is not associated with MS, but it may be associated with higher rates of relapse.27 Minor associations with urinary tract infections and cesarean deliveries with MS in pregnancy have been noted. Although UTI in pregnancy is likely secondary to the sequelae of the disease from neurogenic bladder, the increased incidence of cesarean delivery is possibly due to theoretical concerns for complications or an obstetrician’s decision based on patient fatigue.4 In addition, there are no indications for anesthesia restrictions for patients with MS during labor and delivery.4 MS is not a high-risk condition in pregnancy, but maternal-fetal medicine specialists may be called upon to participate in collaborative care for these patients.
Menopause
Consistent with the literature, providers are uncertain whether menopause is associated with changing MS symptoms. Estrogen seems to provide a protective anti-inflammatory response through inhibition of proinflammatory cytokines and natural killer cell activation.28 As discussed above, estrogen fluctuations often correlate with MS relapses, suggesting the hormone has a neuroprotective effect. Menopause is further confounded by concomitant immunosenescence, leading to a chronic proinflammatory state. The clinical picture of patients with MS in menopause is less clear. Studies have both supported and negated the claim of worsening MS symptoms during menopause, with others pointing toward a transitory aggravation in symptoms.29-31 These studies are complicated by the diagnostic challenge of the overlapping symptoms of MS progression and normal aging with menopause. Hormone replacement therapy (HRT) with combined estrogen-progestogen or estrogen alone is associated with improved quality of life in postmenopausal patients with MS.28 HRT treatment should be considered on an individual basis with the aim of treatment for the shortest possible duration and at the lowest possible dose. Currently, HRT as a neuroprotective agent and hindrance of immunosenescence remains theoretical, although an increased number of B cells, T-cell function, and decreased proinflammatory cytokines have been noted in HRT users.28 Overall, the current evidence indicates that more research is required on this topic.
Strengths and Limitations
To our knowledge, this is the first study to assess OBGYN care providers’ comfort when caring for individuals with MS. A limitation of this study is the applicability of our results to other areas. The majority of our respondents were physicians (85.7%) practicing in an academic setting (68.6%) within a single region who may have more experience with this population, given the higher incidence of MS in the northeastern United States. Additionally, our lower response rate of 29.2% may further skew our results, as those more confident in their knowledge of care may be more likely to participate or complete the survey. Regardless, this study identified gaps in care by OBGYNs that reflect the literature while comprehensively integrating current guidelines on these topics.
Future Directions
Our academic center plans to develop educational content summarizing the literature on OBGYN issues in MS. Through the data generated by this study, we aim to highlight the gaps specific to our institution. This study has also fostered a collaboration between OBGYNs and neurologists. This partnership has not only enriched our research findings but also highlighted the importance of integrated care for patients who may present with overlapping neurologic and gynecologic concerns. Interdisciplinary collaboration is known to improve patient outcomes.32-35 Moving forward, we aim to sustain and strengthen this collaboration to enhance both clinical practice and future research, ultimately improving patient outcomes through a more holistic approach to care. In future studies, we also hope to incorporate feedback from patients with MS and their care partners about unmet needs.
This is the first study to assess the clinical care gaps in the treatment of people with MS by OBGYNs who reported overall poor confidence in caring for them. Providers agreed on recommendations for patients with MS regardless of their years of experience in the field. These recommendations highlight the gaps in the available literature, especially regarding conception, STIs, and menopause, indicating the need for further research to guide clinical management. Future studies should address the accessibility of OBGYN care for this vulnerable population.
Financial Disclosures: Krupa Pandey, MD, has served as a consultant for Biogen, Bristol Myers Squibb, Genentech-Roche, and Sanofi-Genzyme and has served as a speaker for Alexion, Biogen, Bristol Myers Squibb, Genentech-Roche, Horizon Therapeutics, and Sanofi-Genzyme. All other authors have reported no relevant disclosures.
Funding: No sources of funding.
Prior Presentation: A portion of this manuscript’s data regarding menopause recommendations was presented as a poster at the 2023 Menopause Society Annual Meeting; September 27-30, 2023; Philadelphia, Pennsylvania.
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