Periconception care of the infertile patient: Are we doing enough?
In light of advancing experience; greater oversight and involvement in obstetrics; awareness of the interrelation between the multiple epidemics of obesity, diabetes, opioid use; and domestic abuse on skyrocketing rates of maternal morbidity and mortality, author questions whether we as reproductive endocrinologists are doing enough to assess and improve the periconception health of our patients seeking fertility. Furthermore, the increased use of elective oocyte preservation and embryo freeze-all strategies allow us the unique opportunity to take advantage of the youth of the patient for optimal fertility preservation and the gift of time to optimize maternal health before an embryo transfer.
Gynecologists have supported the use of the menstrual history as a vital sign for the health of a woman. Similarly, reproductive endocrinologists (and urologists) have recognized this and infertility per se in patients as a harbinger of underlying, often unrecognized or underappreciated, medical disorders. Now, it is time to take primary responsibility for the periconception health of patients with infertility and address the remedy of these conditions. Gyenocologists as first and foremost specialists in obstetrics and gynecology are obligated to take a broader view of maternal periconception health beyond surrogate subspecialist outcomes. The ultimate goal is a healthy baby and a healthy mother.
There is certainly low hanging fruit that is part of routine preconception care for most reproductive endocrinologists, including obtaining a family history, offering genetic screening, encouraging vaccinations that are absent or no longer effective, and starting folate supplementation. However, the medical conditions most linked to maternal morbidity and mortality and most amenable to preconception intervention are more challenging to correct and often beyond the scope of our daily practice: dysglycemia, hypertension, substance use (tobacco and opioids), and obesity. It has been long recognized that preconception hyperglycemia is a fetal teratogen and that poorly controlled maternal diabetes preconception is a risk factor for both maternal and fetal/infant morbidity. Intervention that lowers ambient glucose levels preconception improves the outcomes.
There are also concerns that lesser degrees of hyperglycemia, such as impaired glucose tolerance, are risk factors for treatment failure and development of gestational diabetes, although the data for preconception treatment with oral agents improving outcomes in this population are weak. Similarly, the data for preconception treatment of substance use disorders such as tobacco or opioids and obesity improving fertility or pregnancy outcomes are weak. However, these data are weak primarily because of a lack of studies in this area.
Most of our resources and research efforts in the past have focused on improving these risk factors with interventions beginning during pregnancy with mixed results. Studies have been able to achieve appropriate gestational weight gain; however, the reward has been slim, with no effect on maternal or perinatal morbidity and mortality beyond reducing the c-section rate. On a positive note, the recent Chronic Hypertension and Pregnancy study showed that pharmacologic treatment of mild chronic hypertension during pregnancy improved both the maternal and neonatal morbidity. Would more aggressive preconception treatment of mild hypertension or impaired glucose tolerance continued throughout the first trimester of pregnancy, or even treatment initiated early in the first trimester, lead to better outcomes?
The limitations of initiating interventions during pregnancy are many. They include certain absolutes. Weight loss during pregnancy in an obese patient is believed to be contraindicated (although that is a basis for a testable hypothesis). There is a reluctance to use unstudied drugs during pregnancy because of unknown fetal effects, which tends to limit the use of newer and more effective treatment agents.
Witness the unwillingness to continue newer opioid therapies such as buprenorphine-naloxone during pregnancy for patients with opioid use disorder. Finally, there is the limitation of the varying time period of presentation of the pregnancy and the relatively short period of pregnancy to correct underlying risk factors.
Most intervention studies during pregnancy begin early in the second trimester, well after gamete formation, fertilization, implantation, and organogenesis. Some believe that the horse of such maternal morbidities as preeclampsia is already out of the barn, especially if preeclampsia is an implantation disorder. The efforts to prevent it with later interventions such as aspirin have been modest at best. Twenty or so weeks of intervention, assuming no preterm delivery, is likely not enough to modify most risk factors enough to move the needle on maternal morbidity and mortality.
Because of their advancing maternal age and underlying medical conditions, the patients are at a greater and potentially additive risk of maternal morbidity and mortality, although no doubt there is also a healthy patient bias in the selection of patients who receive treatment. The recognition of infertility as a disease by the World Health Organization and others (including the American Medical Association and American Society for Reproductive Medicine) does not allow for the cherry picking of patients eligible for care. As more states mandate infertility coverage and the market brings the price of bundled treatment packages down, this healthy patient selection bias will fade.
The opportunities to intervene before conception, early in the first trimester, or after delivery with an American College of Obstetricians and Gynecologists–recommended 18-month interpregnancy window are myriad. Most institutions have a perinatal program to plan for the antepartum, intrapartum, and postpartum care of the mother with a fetus with anomalies, with the emphasis on the fetus and neonate. Why not similar interdisciplinary teams to manage obesity, dysglycemia, hypertension, and substance use disorders in the mother periconception?
Author concludes, "Let it begin with us, let us pilot it for our obstetric colleagues, and remember that at our core, we are also obstetricians. We have largely stopped superovulation/intrauterine insemination and multiple embryo transfer when it was proven that we got higher singleton pregnancy rates and better maternal and infant outcomes with oral ovarian stimulation therapies or elective single-embryo transfer. We have modified our practices to screen women with polycystic ovary syndrome for metabolic abnormalities to comfortably use metformin periconception and have weathered practice changes due to Zika virus and COVID 19. I believe that if we can significantly improve modifiable risk factors periconception (with the emphasis on preconception), we can improve maternal health during and after pregnancy. To end with one of my favorite Chinese proverbs, ''the journey of a thousand miles begins with a single step''. If not us to take the first step, then who?"
Source: Richard S. Legro; Fertility and Sterility
