Periconception care of the infertile patient: Are we doing enough?

Abstract

I lost a Maternal Fetal Medicine departmental colleague of longstanding this week to a sudden and unexpected illness less than a year after his retirement. We joined faculty around the same time 30 years ago, and he would regularly berate me every time I referred a patient with multiple pregnancies (occasionally high order) from superovulation/intrauterine insemination or from multiple cleavage stage embryo transfer for high-risk prenatal care with his group. Similarly, if I sent a patient with obesity and polycystic ovary syndrome to him for preconception counseling, he would drill the patient with the litany of adverse maternal and infant outcomes associated with obesity and urge the patient strongly to defer conception until there was a weight loss. Lighten up I thought (but did not say to him), it is a pipe dream to imagine that most patients will be able to accomplish this goal. It is best to proceed with infertility treatment because, in the grand scheme, we are helping the patient to fulfill their goals and they are aware of the risks.However, 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 our skyrocketing rates of maternal morbidity and mortality, I question whether we as reproductive endocrinologists are doing enough to assess and improve the periconception health of our patients seeking fertility. This has taken on added urgency with the US Supreme Court Dobbs decision likely limiting therapeutic pregnancy termination for maternal morbidity and threatened mortality in so many of our states. 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.We as gynecologists have supported the use of the menstrual history as a vital sign for the health of a woman (1ACOG Committee Opinion No651: Menstruation in girls and adolescents: using the menstrual cycle as a vital sign.Obstet Gynecol. 2015; 126: e143-e146Crossref PubMed Scopus (26) Google Scholar). Similarly, we as reproductive endocrinologists (and urologists) have recognized this and infertility per se in patients as a harbinger of underlying, often unrecognized or underappreciated, medical disorders (2Murugappan G. Li S. Alvero R.J. Luke B. Eisenberg M.L. Association between infertility and all-cause mortality: analysis of US claims data.Am J Obstet Gynecol. 2021; 225: 57 e1-e11Abstract Full Text Full Text PDF Scopus (4) Google Scholar, 3Stentz N.C. Koelper N. Barnhart K.T. Sammel M.D. Senapati S. Infertility and mortality.Am J Obstet Gynecol. 2020; 222: 251 e1-e10Abstract Full Text Full Text PDF Scopus (12) Google Scholar). We have lobbied for funding for further study of these related medical conditions and infertility. Now, it is time to take primary responsibility for the periconception health of our patients with infertility and address the remedy of these conditions. I define periconception as the time period before and through the first trimester of pregnancy, a time period in which we currently are the primary providers for our patients. We as first and foremost specialists in obstetrics and gynecology are obligated to take a broader view of maternal periconception health beyond surrogate subspecialist outcomes. We have seen both clinical trials in infertility (4Harbin Consensus Conference Workshop G. Improving the reporting of clinical trials of infertility treatments (IMPRINT): modifying the CONSORT statement.Fertil Steril. 2014; 102: 952-9 e15Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 5Duffy J.M.N. AlAhwany H. Bhattacharya S. Collura B. Curtis C. Evers J.L.H. et al.Developing a core outcome set for future infertility research: an international consensus development study.Fertil Steril. 2021; 115: 191-200Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar) and Society for Assisted Reproductive Technology statistics move the outcome of interest after treatment from pregnancy test to clinical pregnancy to live birth, while now also capturing all maternal and perinatal morbidity and mortality from both the treatment and ensuing pregnancy. I am sad to say that we as a specialty are much better in following up long-term fetal and infant development after infertility treatment (6Elhakeem A. Taylor A.E. Inskip H.M. Huang J. Tafflet M. Vinther J.L. et al.Association of assisted reproductive technology with offspring growth and adiposity from infancy to early adulthood.J Am Med Assoc Netw Open. 2022; 5e2222106Google Scholar, 7Enova-Veselinovic B. Wijs L.A. Yovich J.L. Burton P. Hart R.J. Cohort profile: the Growing Up Healthy Study (GUHS)-a prospective and observational cohort study investigating the long-term health outcomes of offspring conceived after assisted reproductive technologies.PLoS ONE. 2022; 17e0272064Google Scholar) than capturing maternal morbidity and mortality during pregnancy or long-term maternal health after (or not achieving) pregnancy (8Dapuzzo L. Seitz F.E. Dodson W.C. Stetter C. Kunselman A.R. Legro R.S. Incomplete and inconsistent reporting of maternal and fetal outcomes in infertility treatment trials.Fertil Steril. 2011; 95: 2527-2530Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar). Our 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 (9Collier A.Y. Molina R.L. Maternal mortality in the United States: updates on trends, causes, and solutions.Neoreviews. 2019; 20: e561-e574Crossref PubMed Scopus (40) Google Scholar). We have 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 (10Pedersen L.M. Tygstrup I. Pedersen J. Congenital malformations in newborn infants of diabetic women. Correlation with maternal diabetic vascular complications.Lancet. 1964; 1: 1124-1126Abstract PubMed Google Scholar). Intervention that lowers ambient glucose levels preconception improves the outcomes (11Wahabi H.A. Alzeidan R.A. Esmaeil S.A. Pre-pregnancy care for women with pre-gestational diabetes mellitus: a systematic review and meta-analysis.BMC Public Health. 2012; 12: 792Crossref PubMed Scopus (79) Google Scholar). There are also concerns that lesser degrees of hyperglycemia, such as impaired glucose tolerance, are risk factors for treatment failure (12Wei D. Zhang B. Shi Y. Zhang L. Zhao S. Du Y. et al.Effect of preconception impaired glucose tolerance on pregnancy outcomes in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2017; 102: 3822-3829Crossref PubMed Scopus (15) Google Scholar) and development of gestational diabetes (13Dmitrovic R. Katcher H.I. Kunselman A.R. Legro R.S. Continuous glucose monitoring during pregnancy in women with polycystic ovary syndrome.Obstet Gynecol. 2011; 118: 878-885Crossref PubMed Scopus (17) Google Scholar), although the data for preconception treatment with oral agents improving outcomes in this population are weak (14Løvvik T.S. Carlsen S.M. Salvesen Ø. Steffensen B. Bixo M. Gómez-Real F. et al.Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial.Lancet Diabetes Endocrinol. 2019; 7: 256-266Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar). Similarly, the data for preconception treatment of substance use disorders such as tobacco or opioids (15Boedt T. Vanhove A.C. Vercoe M.A. Matthys C. Dancet E. Lie Fong S. Preconception lifestyle advice for people with infertility.Cochrane Database Syst Rev. 2021; 4: CD008189PubMed Google Scholar) and obesity (15Boedt T. Vanhove A.C. Vercoe M.A. Matthys C. Dancet E. Lie Fong S. Preconception lifestyle advice for people with infertility.Cochrane Database Syst Rev. 2021; 4: CD008189PubMed Google Scholar, 16Syngelaki A. Sequeira Campos M. Roberge S. Andrade W. Nicolaides K.H. Diet and exercise for preeclampsia prevention in overweight and obese pregnant women: systematic review and meta-analysis.J Matern Fetal Neonatal Med. 2019; 32: 3495-3501Crossref PubMed Scopus (18) Google Scholar) 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 (17Goldstein R.F. Abell S.K. Ranasinha S. Misso M.L. Boyle J.A. Harrison C.L. et al.Gestational weight gain across continents and ethnicity: systematic review and meta-analysis of maternal and infant outcomes in more than one million women.BMC Med. 2018; 16: 153Crossref PubMed Scopus (182) Google Scholar). I am not aware of any data on smoking cessation or reduction during pregnancy improving any fetal or maternal outcome either. 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 (18Tita A.T. Szychowski J.M. Boggess K. Dugoff L. Sibai B. Lawrence K. et al.Treatment for mild chronic hypertension during pregnancy.N Engl J Med. 2022; 386: 1781-1792Crossref PubMed Scopus (36) Google Scholar). 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 (19Waite L.L. Atwood A.K. Taylor R.N. Preeclampsia, an implantation disorder.Rev Endocr Metab Disord. 2002; 3: 151-158Crossref PubMed Scopus (25) Google Scholar). Our efforts to prevent it with later interventions such as aspirin have been modest at best (19Waite L.L. Atwood A.K. Taylor R.N. Preeclampsia, an implantation disorder.Rev Endocr Metab Disord. 2002; 3: 151-158Crossref PubMed Scopus (25) Google Scholar, 20Rolnik D.L. Nicolaides K.H. Poon L.C. Prevention of preeclampsia with aspirin.Am J Obstet Gynecol. 2022; 226: S1108-S1119Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). 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, our patients are at a greater and potentially additive risk of maternal morbidity and mortality (21Brown H.K. McKnight A. Aker A. Association between pre-pregnancy multimorbidity and adverse maternal outcomes: a systematic review.J Multimorb Comorb. 2022; 1226335565221096584Crossref PubMed Google Scholar), although no doubt there is also a healthy patient bias in the selection of patients who receive treatment (22Vassard D. Schmidt L. Pinborg A. Petersen G.L. Forman J.L. Hageman I. et al.Mortality in women treated with assisted reproductive technology-addressing the healthy patient effect.Am J Epidemiol. 2018; 187: 1889-1895Crossref PubMed Scopus (14) Google Scholar). 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. Optimizing health periconception should be a goal of specialists in all fields; however, our specialist colleagues in obstetrics face the dilemma that approximately 50% of pregnancies are unplanned (23Finer L.B. Zolna M.R. Declines in unintended pregnancy in the United States, 2008-2011.N Engl J Med. 2016; 374: 843-852Crossref PubMed Scopus (1215) Google Scholar). We have the opportunity of seeing patients who 100% are planning pregnancy and, in general, committed to change to achieve that goal.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 (24American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Obstetric care consensus no. 8: interpregnancy care.Obstet Gynecol. 2019; : 133:e51-e72PubMed Google Scholar). I question why there are no established interdisciplinary programs to optimize maternal health during these time periods. 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 (25D'Alton M.E. Friedman A.M. Bernstein P.S. Brown H.L. Callaghan W.M. Clark S.L. et al.Putting the "M" back in maternal-fetal medicine: a 5-year report card on a collaborative effort to address maternal morbidity and mortality in the United States.Am J Obstet Gynecol. 2019; 221: 311-7 e1Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar)? Although currently only a fraction (2%–5%) of deliveries in the United States result from infertility therapy (26Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies.Am J Obstet Gynecol. 2017; 217: 270-281Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar), we have a motivated and easily identified (note that I avoided the word “captive”) patient population and one, when further enriched by equitable access to infertility treatment, will have a surplus of modifiable risk factors for maternal and perinatal morbidity and mortality.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? I lost a Maternal Fetal Medicine departmental colleague of longstanding this week to a sudden and unexpected illness less than a year after his retirement. We joined faculty around the same time 30 years ago, and he would regularly berate me every time I referred a patient with multiple pregnancies (occasionally high order) from superovulation/intrauterine insemination or from multiple cleavage stage embryo transfer for high-risk prenatal care with his group. Similarly, if I sent a patient with obesity and polycystic ovary syndrome to him for preconception counseling, he would drill the patient with the litany of adverse maternal and infant outcomes associated with obesity and urge the patient strongly to defer conception until there was a weight loss. Lighten up I thought (but did not say to him), it is a pipe dream to imagine that most patients will be able to accomplish this goal. It is best to proceed with infertility treatment because, in the grand scheme, we are helping the patient to fulfill their goals and they are aware of the risks. However, 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 our skyrocketing rates of maternal morbidity and mortality, I question whether we as reproductive endocrinologists are doing enough to assess and improve the periconception health of our patients seeking fertility. This has taken on added urgency with the US Supreme Court Dobbs decision likely limiting therapeutic pregnancy termination for maternal morbidity and threatened mortality in so many of our states. 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. We as gynecologists have supported the use of the menstrual history as a vital sign for the health of a woman (1ACOG Committee Opinion No651: Menstruation in girls and adolescents: using the menstrual cycle as a vital sign.Obstet Gynecol. 2015; 126: e143-e146Crossref PubMed Scopus (26) Google Scholar). Similarly, we as reproductive endocrinologists (and urologists) have recognized this and infertility per se in patients as a harbinger of underlying, often unrecognized or underappreciated, medical disorders (2Murugappan G. Li S. Alvero R.J. Luke B. Eisenberg M.L. Association between infertility and all-cause mortality: analysis of US claims data.Am J Obstet Gynecol. 2021; 225: 57 e1-e11Abstract Full Text Full Text PDF Scopus (4) Google Scholar, 3Stentz N.C. Koelper N. Barnhart K.T. Sammel M.D. Senapati S. Infertility and mortality.Am J Obstet Gynecol. 2020; 222: 251 e1-e10Abstract Full Text Full Text PDF Scopus (12) Google Scholar). We have lobbied for funding for further study of these related medical conditions and infertility. Now, it is time to take primary responsibility for the periconception health of our patients with infertility and address the remedy of these conditions. I define periconception as the time period before and through the first trimester of pregnancy, a time period in which we currently are the primary providers for our patients. We as first and foremost specialists in obstetrics and gynecology are obligated to take a broader view of maternal periconception health beyond surrogate subspecialist outcomes. We have seen both clinical trials in infertility (4Harbin Consensus Conference Workshop G. Improving the reporting of clinical trials of infertility treatments (IMPRINT): modifying the CONSORT statement.Fertil Steril. 2014; 102: 952-9 e15Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 5Duffy J.M.N. AlAhwany H. Bhattacharya S. Collura B. Curtis C. Evers J.L.H. et al.Developing a core outcome set for future infertility research: an international consensus development study.Fertil Steril. 2021; 115: 191-200Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar) and Society for Assisted Reproductive Technology statistics move the outcome of interest after treatment from pregnancy test to clinical pregnancy to live birth, while now also capturing all maternal and perinatal morbidity and mortality from both the treatment and ensuing pregnancy. I am sad to say that we as a specialty are much better in following up long-term fetal and infant development after infertility treatment (6Elhakeem A. Taylor A.E. Inskip H.M. Huang J. Tafflet M. Vinther J.L. et al.Association of assisted reproductive technology with offspring growth and adiposity from infancy to early adulthood.J Am Med Assoc Netw Open. 2022; 5e2222106Google Scholar, 7Enova-Veselinovic B. Wijs L.A. Yovich J.L. Burton P. Hart R.J. Cohort profile: the Growing Up Healthy Study (GUHS)-a prospective and observational cohort study investigating the long-term health outcomes of offspring conceived after assisted reproductive technologies.PLoS ONE. 2022; 17e0272064Google Scholar) than capturing maternal morbidity and mortality during pregnancy or long-term maternal health after (or not achieving) pregnancy (8Dapuzzo L. Seitz F.E. Dodson W.C. Stetter C. Kunselman A.R. Legro R.S. Incomplete and inconsistent reporting of maternal and fetal outcomes in infertility treatment trials.Fertil Steril. 2011; 95: 2527-2530Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar). Our 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 (9Collier A.Y. Molina R.L. Maternal mortality in the United States: updates on trends, causes, and solutions.Neoreviews. 2019; 20: e561-e574Crossref PubMed Scopus (40) Google Scholar). We have 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 (10Pedersen L.M. Tygstrup I. Pedersen J. Congenital malformations in newborn infants of diabetic women. Correlation with maternal diabetic vascular complications.Lancet. 1964; 1: 1124-1126Abstract PubMed Google Scholar). Intervention that lowers ambient glucose levels preconception improves the outcomes (11Wahabi H.A. Alzeidan R.A. Esmaeil S.A. Pre-pregnancy care for women with pre-gestational diabetes mellitus: a systematic review and meta-analysis.BMC Public Health. 2012; 12: 792Crossref PubMed Scopus (79) Google Scholar). There are also concerns that lesser degrees of hyperglycemia, such as impaired glucose tolerance, are risk factors for treatment failure (12Wei D. Zhang B. Shi Y. Zhang L. Zhao S. Du Y. et al.Effect of preconception impaired glucose tolerance on pregnancy outcomes in women with polycystic ovary syndrome.J Clin Endocrinol Metab. 2017; 102: 3822-3829Crossref PubMed Scopus (15) Google Scholar) and development of gestational diabetes (13Dmitrovic R. Katcher H.I. Kunselman A.R. Legro R.S. Continuous glucose monitoring during pregnancy in women with polycystic ovary syndrome.Obstet Gynecol. 2011; 118: 878-885Crossref PubMed Scopus (17) Google Scholar), although the data for preconception treatment with oral agents improving outcomes in this population are weak (14Løvvik T.S. Carlsen S.M. Salvesen Ø. Steffensen B. Bixo M. Gómez-Real F. et al.Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial.Lancet Diabetes Endocrinol. 2019; 7: 256-266Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar). Similarly, the data for preconception treatment of substance use disorders such as tobacco or opioids (15Boedt T. Vanhove A.C. Vercoe M.A. Matthys C. Dancet E. Lie Fong S. Preconception lifestyle advice for people with infertility.Cochrane Database Syst Rev. 2021; 4: CD008189PubMed Google Scholar) and obesity (15Boedt T. Vanhove A.C. Vercoe M.A. Matthys C. Dancet E. Lie Fong S. Preconception lifestyle advice for people with infertility.Cochrane Database Syst Rev. 2021; 4: CD008189PubMed Google Scholar, 16Syngelaki A. Sequeira Campos M. Roberge S. Andrade W. Nicolaides K.H. Diet and exercise for preeclampsia prevention in overweight and obese pregnant women: systematic review and meta-analysis.J Matern Fetal Neonatal Med. 2019; 32: 3495-3501Crossref PubMed Scopus (18) Google Scholar) 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 (17Goldstein R.F. Abell S.K. Ranasinha S. Misso M.L. Boyle J.A. Harrison C.L. et al.Gestational weight gain across continents and ethnicity: systematic review and meta-analysis of maternal and infant outcomes in more than one million women.BMC Med. 2018; 16: 153Crossref PubMed Scopus (182) Google Scholar). I am not aware of any data on smoking cessation or reduction during pregnancy improving any fetal or maternal outcome either. 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 (18Tita A.T. Szychowski J.M. Boggess K. Dugoff L. Sibai B. Lawrence K. et al.Treatment for mild chronic hypertension during pregnancy.N Engl J Med. 2022; 386: 1781-1792Crossref PubMed Scopus (36) Google Scholar). 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 (19Waite L.L. Atwood A.K. Taylor R.N. Preeclampsia, an implantation disorder.Rev Endocr Metab Disord. 2002; 3: 151-158Crossref PubMed Scopus (25) Google Scholar). Our efforts to prevent it with later interventions such as aspirin have been modest at best (19Waite L.L. Atwood A.K. Taylor R.N. Preeclampsia, an implantation disorder.Rev Endocr Metab Disord. 2002; 3: 151-158Crossref PubMed Scopus (25) Google Scholar, 20Rolnik D.L. Nicolaides K.H. Poon L.C. Prevention of preeclampsia with aspirin.Am J Obstet Gynecol. 2022; 226: S1108-S1119Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). 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, our patients are at a greater and potentially additive risk of maternal morbidity and mortality (21Brown H.K. McKnight A. Aker A. Association between pre-pregnancy multimorbidity and adverse maternal outcomes: a systematic review.J Multimorb Comorb. 2022; 1226335565221096584Crossref PubMed Google Scholar), although no doubt there is also a healthy patient bias in the selection of patients who receive treatment (22Vassard D. Schmidt L. Pinborg A. Petersen G.L. Forman J.L. Hageman I. et al.Mortality in women treated with assisted reproductive technology-addressing the healthy patient effect.Am J Epidemiol. 2018; 187: 1889-1895Crossref PubMed Scopus (14) Google Scholar). 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. Optimizing health periconception should be a goal of specialists in all fields; however, our specialist colleagues in obstetrics face the dilemma that approximately 50% of pregnancies are unplanned (23Finer L.B. Zolna M.R. Declines in unintended pregnancy in the United States, 2008-2011.N Engl J Med. 2016; 374: 843-852Crossref PubMed Scopus (1215) Google Scholar). We have the opportunity of seeing patients who 100% are planning pregnancy and, in general, committed to change to achieve that goal. 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 (24American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Obstetric care consensus no. 8: interpregnancy care.Obstet Gynecol. 2019; : 133:e51-e72PubMed Google Scholar). I question why there are no established interdisciplinary programs to optimize maternal health during these time periods. 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 (25D'Alton M.E. Friedman A.M. Bernstein P.S. Brown H.L. Callaghan W.M. Clark S.L. et al.Putting the "M" back in maternal-fetal medicine: a 5-year report card on a collaborative effort to address maternal morbidity and mortality in the United States.Am J Obstet Gynecol. 2019; 221: 311-7 e1Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar)? Although currently only a fraction (2%–5%) of deliveries in the United States result from infertility therapy (26Luke B. Pregnancy and birth outcomes in couples with infertility with and without assisted reproductive technology: with an emphasis on US population-based studies.Am J Obstet Gynecol. 2017; 217: 270-281Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar), we have a motivated and easily identified (note that I avoided the word “captive”) patient population and one, when further enriched by equitable access to infertility treatment, will have a surplus of modifiable risk factors for maternal and perinatal morbidity and mortality. 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?