Publications Committee 

Assisted reproductive technology (ART) now accounts for 1.6% of all infants and 18.3% of all multiple-birth infants in the United States.

 Although most of these pregnancies are uncomplicated, IVF is associated with several adverse maternal and perinatal outcomes. This Consult discusses the management of pregnancies achieved with in vitro fertilization and provides recommendations based on the available evidence.

What genetic conditions should be discussed for patients considering or who have undergone IVF?

The IVF procedure itself does not appear to lead to a higher prevalence of chromosomal anomalies when compared with naturally occurring pregnancy.

 However, a significantly increased rate of de-novo chromosomal abnormalities has been reported in ICSI pregnancies compared with a reference group of naturally occurring pregnancies or the general population.

Other factors may play a role in the increased risk of chromosomal anomalies in IVF pregnancies, including advanced maternal age, polycystic ovary syndrome,

 and severe male and female factor infertility. Imprinting syndromes, including Beckwith-Wiedemann syndrome (BWS),

Angelman/Prader Willi syndrome (PWS), and Russell-Silver syndrome,

are thought to occur more frequently in the offspring of subfertile parents,

although the absolute risk remains small. 

Patients with reduced ovarian reserve and primary ovarian insufficiency have an increased risk of being full mutation or premutation carriers of fragile X.These patients typically undergo 

 gene testing before undergoing IVF. Preimplantation genetic testing should be offered for monogenic disorders with the transfer of only embryos carrying the normal X chromosome.

We suggest genetic counseling be offered to all patients undergoing or who have undergone IVF with or without ICSI (GRADE 2C)

What are the different types of preimplantation genetic testing?

The types of preimplantation genetic testing (PFT) are as follows:

PGT for aneuploidy (PGT-A): Its value as a screening test for IVF patients has been debated.

 It does not replace the recommendation for prenatal screening or diagnosis.

Preimplantation genetic testing for monogenic disorders (PGT-M): It is used most commonly in couples with previous offspring affected by single-gene disorders (such as cystic fibrosis) or who have undergone carrier screening with both partners testing positive for a mutation associated with a genetic disease.

Preimplantation genetic testing for structural [chromosomal] rearrangements (PGT-SR):This testing is usually performed when one partner is known to be a carrier of a balanced translocation or a deletion or duplication.

For both PGT-M and PGT-SR, it is recommended that a confirmatory diagnostic test be offered during the pregnancy.

Many patients, however, do not wish to pursue invasive testing after PGT.

Regardless of whether PGT has been performed, we recommend that all patients who have achieved pregnancy with IVF be offered the options of prenatal genetic screening and diagnostic testing via chorionic villus sampling or amniocentesis (GRADE 1C).

If euploid embryos are unavailable, aneuploid mosaic embryos are sometimes transferred.

 Prenatal diagnostic testing should be offered to patients with pregnancies that occur from transferring an embryo with a mosaic trisomy or monosomy. Consultation with a genetic counselor or geneticist can be offered to discuss diagnostic testing for these patients. Screening with cell-free DNA (cfDNA) has limited clinical utility in this setting.

What is the accuracy of first-trimester genetic screening tests in IVF pregnancies?

The accuracy of first-trimester genetic screening tests for aneuploidies may be affected by IVF, with a potential increased risk of false-positive results for aneuploidies in patients who undergo first trimester combined screening.

Lower fetal fraction (FF) has been reported with cfDNA in IVF pregnancies,

 leading to higher rates of failed cfDNA results compared with naturally occurring pregnancies. However, IVF does not appear to be a risk factor for failed results on repeat cfDNA testing (second draw).

We recommend that the accuracy of first-trimester screening tests, including cfDNA for aneuploidy, be discussed with patients undergoing or who have undergone IVF (GRADE 1A).

Does multifetal pregnancy reduction reduce the risks associated with multiple gestations?

Given the increase in maternal and perinatal morbidity and mortality associated with twins and higher-order multifetal pregnancies,27 efforts should be made to limit multifetal pregnancies during ART. However, even when a single embryo is transferred, the risk of monozygotic twins is increased. 

When multifetal pregnancies do occur, we recommend counseling be offered regarding the option of multifetal pregnancy reduction (GRADE 1C).

Multifetal pregnancy reduction has been shown to significantly reduce the risks of preterm birth, neonatal morbidity, and maternal complications.

Are congenital anomalies increased in IVF pregnancies?

Meta-analyses demonstrate associations between IVF/ICSI and congenital malformations, although it remains unclear if this association is due to infertility, factors associated with the procedure, or both.

It is also difficult to distinguish the risk associated with IVF alone versus IVF with ICSI. 

 we recommend a detailed obstetrical ultrasound examination (CPT 76811) be performed for pregnancies achieved with IVF and ICSI (GRADE 1B).

Several studies report higher rates of total congenital heart disease (CHD) in the IVF/ICSI population compared with naturally occurring pregnancies, while other studies report that the incidence of CHD in IVF pregnancies without other risk factors is not significantly different from baseline population rates 34The cost-effectiveness of routine screening for CHD in pregnancies following IVF has also been questioned.

We suggest fetal echocardiography be offered to patients with pregnancies achieved with IVF and ICSI (GRADE 2C).

Are placental anomalies increased in IVF pregnancies?

IVF pregnancies are associated with higher risks for abnormal placental shape (bilobed placenta, accessory placental lobes), placenta previa, marginal or velamentous cord insertion, and placenta accreta spectrum compared with naturally occurring pregnancies. 

All of the above manifestations of placental implantation disorders appear related and can occur together. 

, we recommend a careful examination of the placental location, placental shape, and cord insertion site be performed at the time of the detailed fetal anatomy ultrasound, including evaluation for vasa previa (GRADE 1B).

Targeted screening via transvaginal sonogram should be considered in all IVF pregnancies with velamentous cord insertion, succenturiate or bilobed placentas, or resolved placenta previa to rule out vasa previa.

 Due to the ongoing risk of vasa previa in the setting of resolved placenta previa, reassessment for vasa previa is warranted when reassessing placental location at 32 weeks of gestation.

Is the prevalence of spontaneous preterm birth higher in IVF pregnancies?

A meta-analysis of singleton pregnancies demonstrated that IVF is associated with higher odds of preterm delivery, low birthweight, and very low birthweight compared with naturally occurring pregnancies.

Preterm birth has been recognized for several decades as the primary independent cause of increased rates of several adverse neonatal outcomes, including neonatal encephalopathy and perinatal mortality, in IVF pregnancies. 

Such risks are more than doubled in the presence of IVF twin gestations. Subfertility is also a major risk factor for prematurity.

 Although there may be an increased risk for spontaneous preterm birth with IVF pregnancies, the utility of serial cervical length measurement to screen for preterm birth risk is unknown when the sole indication is IVF.

Although visualization of the cervix at the 18 0/7 to 22 6/7 weeks of gestation anatomy assessment with either a transabdominal or endovaginal approach is recommended, we do not recommend serial cervical length assessment as a routine practice for IVF pregnancies (GRADE 1C).

In addition, progesterone supplementation initiated for IVF cycles is not indicated after 12 weeks of gestation if it was solely initiated for IVF purposes without any other indication. Discontinuation of progesterone supplementation initiated for the sole purpose of IVF is recommended by 12 weeks.

Is the prevalence of fetal growth restriction higher in IVF pregnancies?

An increased risk of small for gestational age (SGA) infants is documented for singleton IVF pregnancies. Meta-analyses have described a higher risk of SGA babies in IVF/ICSI pregnancies from fresh cycles compared with frozen cycles.

The optimal gestational ages for fetal growth scans and their frequency in the presence of additional risk factors (eg, placental implantation anomalies or maternal age >40 years) are presently unknown. 

We suggest an assessment of fetal growth in the third trimester for IVF pregnancies; however, serial growth ultrasounds are not recommended for the sole indication of IVF (GRADE 2B).

In pregnancies achieved with IVF, does low-dose aspirin prophylaxis reduce the risk of fetal and placental complications?

IVF and underlying infertility are associated with adverse perinatal outcomes, including hypertensive disorders of pregnancy.

 The United States Preventative Services Task Force states IVF is a moderate risk factor for preeclampsia and recommends low-dose aspirin if an additional moderate risk factor is found.

We do not recommend low-dose aspirin in patients with an IVF pregnancy as the sole indication for preeclampsia prophylaxis; however, if one or more additional risk factors are present, low-dose aspirin is recommended (GRADE 1B).

Is the prevalence of stillbirth increased in IVF pregnancies?

Pregnancies achieved with IVF have a two to three-fold increased risk of stillbirth even after controlling for maternal age, parity, and multifetal gestations.

Given the increased risk of stillbirth, we suggest weekly antenatal fetal surveillance beginning by 36 0/7 weeks of gestation

for pregnancies achieved with IVF (GRADE 2C).

In pregnancies achieved with IVF, does delivery at 39 weeks reduce the risk of adverse perinatal outcomes?

It is currently unknown whether elective delivery at 39 weeks reduces the risks of maternal morbidity and improves perinatal outcomes in IVF pregnancies compared with expectant management. 

A systematic review revealed that in asymptomatic uncomplicated singleton gestations, induction of labor between 39 0/7 and 40 6/7 weeks does not increase the risk of cesarean delivery compared with expectant management but does not reduce the rates of adverse perinatal outcomes, including perinatal death, low Apgar score at 5 minutes, or need for NICU admission.

In the absence of studies focused specifically on timing of deliveryIVF pregnancies, we recommend shared decision-making between patients and healthcare providers when considering induction of labor at 39 weeks of gestation (GRADE 1C).

IVF is associated with an increased risk of adverse maternal and perinatal outcomes. However, evidence is limited regarding whether specific screening, diagnostic, or preventative interventions during pregnancy obviate or reduce such risks. Specific technical characteristics of IVF and the presence of underlying infertilityaffect the risks of adverse clinical outcomes. Therefore, individualization of care may be ideal for optimizing outcomes.

Summary of Recommendations

1.Sunderam S, Kissin DM, Crawford SB, et al. Assisted Reproductive Technology Surveillance - United States, 2014. MMWR Surveill Summ 2017;66(6):1-24. (In eng). DOI: 10.15585/mmwr.ss6606a1.

2.Conway DA, Patel SS, Liem J, et al. The risk of cytogenetic abnormalities in the late first trimester of pregnancies conceived through assisted reproduction. Fertil Steril 2011;95(2):503-6. (In eng). DOI: 10.1016/j.fertnstert.2010.09.019.

3.Shevell T, Malone FD, Vidaver J, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 2005;106(5 Pt 1):1039-45. (In eng). DOI: 10.1097/01.AOG.0000183593.24583.7c.

4.Aboulghar H, Aboulghar M, Mansour R, Serour G, Amin Y, Al-Inany H. A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection. Fertil Steril 2001;76(2):249-53. (In eng). DOI: 10.1016/s0015-0282(01)01927-6.

5.Bonduelle M, Van Assche E, Joris H, et al. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod 2002;17(10):2600-14. (In eng). DOI: 10.1093/humrep/17.10.2600.

6.Hong KH, Franasiak JM, Werner MM, et al. Embryonic aneuploidy rates are equivalent in natural cycles and gonadotropin-stimulated cycles. Fertil Steril 2019;112(4):670-676. (In eng). DOI: 10.1016/j.fertnstert.2019.05.039.

7.Li Y, Wang L, Xu J, et al. Higher chromosomal aberration rate in miscarried conceptus from polycystic ovary syndrome women undergoing assisted reproductive treatment. Fertil Steril 2019;111(5):936-943.e2. (In eng). DOI: 10.1016/j.fertnstert.2019.01.026.

8.DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet 2003;72(1):156-60. (In eng). DOI: 10.1086/346031.

9.Gicquel C, Gaston V, Mandelbaum J, Siffroi JP, Flahault A, Le Bouc Y. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet 2003;72(5):1338-41. (In eng). DOI: 10.1086/374824.

10.Halliday J, Oke K, Breheny S, Algar E, D JA. Beckwith-Wiedemann syndrome and IVF: a case-control study. Am J Hum Genet 2004;75(3):526-8. (In eng). DOI: 10.1086/423902.

11.Vermeiden JP, Bernardus RE. Are imprinting disorders more prevalent after human in vitro fertilization or intracytoplasmic sperm injection? Fertil Steril 2013;99(3):642-51. (In eng). DOI: 10.1016/j.fertnstert.2013.01.125.

12.Hattori H, Hiura H, Kitamura A, et al. Association of four imprinting disorders and ART. Clin Epigenetics 2019;11(1):21. (In eng). DOI: 10.1186/s13148-019-0623-3.

13.Uk A, Collardeau-Frachon S, Scanvion Q, Michon L, Amar E. Assisted Reproductive Technologies and imprinting disorders: Results of a study from a French congenital malformations registry. Eur J Med Genet 2018;61(9):518-523. (In eng). DOI: 10.1016/j.ejmg.2018.05.017.

14.Gosden R, Trasler J, Lucifero D, Faddy M. Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet 2003;361(9373):1975-7. (In eng). DOI: 10.1016/s0140-6736(03)13592-1.

15.Haham LM, Avrahami I, Domniz N, et al. Preimplantation genetic diagnosis versus prenatal diagnosis-decision-making among pregnant FMR1 premutation carriers. J Assist Reprod Genet 2018;35(11):2071-2075. (In eng). DOI: 10.1007/s10815-018-1293-3.

16.Pastore LM, Christianson MS, McGuinness B, Vaught KC, Maher JY, Kearns WG. Does theFMR1 gene affect IVF success? Reprod Biomed Online 2019;38(4):560-569. (In eng). DOI: 10.1016/j.rbmo.2018.11.009.

17.Katagiri Y, Tamaki Y. Genetic counseling prior to assisted reproductive technology. Reprod Med Biol 2021;20(2):133-143. (In eng). DOI: 10.1002/rmb2.12361.

18.Gleicher N, Albertini DF, Barad DH, et al. The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A. Reprod Biol Endocrinol 2020;18(1):57. (In eng). DOI: 10.1186/s12958-020-00616-w.

19.Sciorio R, Dattilo M. PGT-A preimplantation genetic testing for aneuploidies and embryo selection in routine ART cycles: Time to step back? Clin Genet 2020;98(2):107-115. (In eng). DOI: 10.1111/cge.13732.

20.Carson SA, Kallen AN. Diagnosis and Management of Infertility: A Review. Jama 2021;326(1):65-76. (In eng). DOI: 10.1001/jama.2021.4788.

21.Preimplantation Genetic Testing: ACOG Committee Opinion, Number 799. Obstet Gynecol 2020;135(3):e133-e137. (In eng). DOI: 10.1097/aog.0000000000003714.

22.Greco E, Minasi MG, Fiorentino F. Healthy Babies after Intrauterine Transfer of Mosaic Aneuploid Blastocysts. N Engl J Med 2015;373(21):2089-90. (In eng). DOI: 10.1056/NEJMc1500421.

23.Clinical management of mosaic results from preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion. Fertil Steril 2020;114(2):246-254. (In eng). DOI: 10.1016/j.fertnstert.2020.05.014.

24.Gjerris AC, Tabor A, Loft A, Christiansen M, Pinborg A. First trimester prenatal screening among women pregnant after IVF/ICSI. Hum Reprod Update 2012;18(4):350-9. (In eng). DOI: 10.1093/humupd/dms010.

25.Rizzo G, Aiello E, Pietrolucci ME, Arduini D. Are There Differences in Placental Volume and Uterine Artery Doppler in Pregnancies Resulting From the Transfer of Fresh Versus Frozen-Thawed Embryos Through In Vitro Fertilization. Reprod Sci 2016;23(10):1381-6. (In eng). DOI: 10.1177/1933719116641765.

26.White K, Wang Y, Kunz LH, Schmid M. Factors associated with obtaining results on repeat cell-free DNA testing in samples redrawn due to insufficient fetal fraction. J Matern Fetal Neonatal Med 2019:1-6. (In eng). DOI: 10.1080/14767058.2019.1594190.

27.Qin JB, Sheng XQ, Wang H, et al. Worldwide prevalence of adverse pregnancy outcomes associated with in vitro fertilization/intracytoplasmic sperm injection among multiple births: a systematic review and meta-analysis based on cohort studies. Arch Gynecol Obstet 2017;295(3):577-597. (In eng). DOI: 10.1007/s00404-017-4291-2.

28.Committee Opinion No. 719: Multifetal Pregnancy Reduction. Obstet Gynecol 2017;130(3):e158-e163. (In eng). DOI: 10.1097/aog.0000000000002302.

29.Hviid KVR, Malchau SS, Pinborg A, Nielsen HS. Determinants of monozygotic twinning in ART: a systematic review and a meta-analysis. Hum Reprod Update 2018;24(4):468-483. (In eng). DOI: 10.1093/humupd/dmy006.

30.Chen L, Yang T, Zheng Z, Yu H, Wang H, Qin J. Birth prevalence of congenital malformations in singleton pregnancies resulting from in vitro fertilization/intracytoplasmic sperm injection worldwide: a systematic review and meta-analysis. Arch Gynecol Obstet 2018;297(5):1115-1130. (In eng). DOI: 10.1007/s00404-018-4712-x.

31.Hoorsan H, Mirmiran P, Chaichian S, Moradi Y, Hoorsan R, Jesmi F. Congenital Malformations in Infants of Mothers Undergoing Assisted Reproductive Technologies: A Systematic Review and Meta-analysis Study. J Prev Med Public Health 2017;50(6):347-360. (In eng). DOI: 10.3961/jpmph.16.122.

32.Wen J, Jiang J, Ding C, et al. Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril 2012;97(6):1331-7.e1-4. (In eng). DOI: 10.1016/j.fertnstert.2012.02.053.

Articles

This Consult discusses the management of pregnancies achieved with in vitro fertilization and provides recommendations based on the available evidence. 

SMFM Consult Series #60: Management of pregnancies resulting from IVF

Reproductive planning is essential for all women and most important for those with complex health conditions or at high risk for complications. Medically complex women are at increased risk for unintended pregnancy compared to a healthy cohort, and for these women, an unintended pregnancy in the setting of poor disease control could increase risk of adverse pregnancy outcomes, disease progression, fetal compromise, or long-term childhood health issues. The postpartum period is an especially vulnerable time, as 70% of pregnancies that occur within 1 year of delivery are unplanned. Interpregnancy intervals shorter than 6 months are associated with increased risks of preterm birth, low birth weight, and small for gestational age infants.

Despite the need for pregnancy planning, medically complex women face many barriers to contraceptive use. Providing contraceptive counseling and a full range of contraceptive options, including immediate postpartum long-acting reversible contraception (LARC), is a means of overcoming these barriers. 

LARC methods include hormonal and nonhormonal intrauterine devices (IUDs) as well as subdermal contraceptive implants. In the United States, the levonorgestrel intrauterine system (IUS) is available in several commercial preparations (Liletta, Mirena, Kyleena, and Skyla), and the nonhormonal copper IUD is commercially available as Paragard. The etonogestrel implant is commercially known as Nexplanon.

What is the role of contraception in the care of high-risk women? 

The interconception period is a time that allows for optimization of maternal health. Contraception facilitates adequate birth spacing to achieve this goal. This is particularly important for women with comorbid conditions or who have had a complication during pregnancy. The most effective way to prevent an unintended pregnancy is through consistent and correct use of contraception.

What is the role of LARC in reproductive planning in medically complex women?  

The American College of Obstetricians and Gynecologists (ACOG) recommends that LARC methods be offered to all appropriate candidates. LARC methods have low failure rates, similar to those of sterilization, making them appealing to women for whom future pregnancy is not recommended or when sterilization is not an option. For medically complex women, LARC methods provide the benefit of allowing a pregnancy to occur in a well-planned and highly supervised medical setting for women in whom an unplanned pregnancy would pose a high medical risk. The long-acting nature of LARC allows women to optimize chronic health conditions prior to conception, but LARC methods remain easily reversible when pregnancy is desired. LARC methods do not contain estrogen, making them safe options for women with a history of medical conditions, such as thromboembolic disease, for whom estrogen is contraindicated. 

Immediate postpartum placement is defined as insertion of an IUD after placental delivery following a vaginal or cesarean delivery and insertion of an implant at any time during the delivery hospitalization.

 When should providers discuss immediate postpartum contraception?

Contraceptive counseling should begin early in pregnancy, be individualized, include a balanced discussion about the risks and benefits of all contraceptive methods, and use shared decision-making. Incorporating contraceptive counseling into prenatal care can contribute substantially to a woman’s health long after pregnancy. This should be an ongoing discussion during the prenatal period, as complications can develop during pregnancy that may have an impact on contraceptive counseling.

 What are the benefits of immediate postpartum LARC insertion?   

LARC is a safe, convenient, and effective option for postpartum contraception that can be placed immediately after delivery. It provides immediate contraception without breastfeeding interference and avoids the discomfort related to later IUD insertion. Compared with short-acting methods, use of immediate postpartum LARC results in increased short-term contraceptive use, similar or increased long-term contraceptive use, and decreased prevalence of short interpregnancy intervals and rates of unintended pregnancy. Compared with other interval insertions of LARC methods, immediate postpartum placement is associated with high patient satisfaction and acceptability, increased method continuation, and superior cost-effectiveness. 

 Which LARC methods are appropriate for women at high risk for complications?  

Obstetric care providers can use the U.S. Medical Eligibility Criteria for Contraceptive Use (

) to counsel medically complex women on individualized, efficacious, and evidence-based contraceptive options. 

The US MEC also makes recommendations specific to the immediate postpartum period, and LARC methods are category 1 or 2 for most conditions. With few exceptions, immediate postpartum LARC is an option regardless of medical complexity. A summary chart of the USMEC for contraceptive use is available on the US Centers for Disease Control and Prevention 

 as well as in an app for smartphones and tablets (“Contraception”).

What are the contraindications to immediate postpartum LARC? 

The few contraindications to immediate postpartum LARC placement are similar to those for interval LARC placement and are listed in the US MEC. Clinical recommendations and medical contraindications to LARC in the US MEC also apply to the immediate postpartum period. 

 What are the risks of immediate postpartum IUD placement?

Most risks are similar between immediate postpartum IUD insertion and insertion at other times, with the exception of expulsion, which has a higher risk. Expulsion rates of 2%, 10%, and 25% have been reported with immediate postpartum placement compared with expulsion rates of 2% with 6-week postpartum IUD placement. The expulsion risk may influence LARC choice for some women. Although immediate postpartum IUD placement has higher expulsion rates than interval placement, the benefits of immediate placement appear to outweigh the drawbacks. A review of seven studies shows that even with higher expulsion rates, women who had immediate postpartum IUD placement were more likely to continue to use the IUD at 6 months than those who had an IUD inserted at another time.

What is the technique for immediate postpartum LARC placement?  

Several techniques of immediate postpartum LARC placement following vaginal and cesarean delivery are described, using either a ring or Kelly placental forceps, manual insertion with the operator’s hand, or the manufacturer’s inserter. ACOG suggests that providers receive formal training to enable appropriate immediate postpartum IUD placement after cesarean and vaginal deliveries. LARC method-specific training opportunities are available on the ACOG 

The technique for immediate postpartum contraceptive implant insertion is the same used in other settings and at other times. Insertion can be achieved in the labor and delivery unit or in the postpartum unit. The US Food and Drug Administration requires that obstetric care providers receive training provided by the manufacturer.

Does immediate postpartum LARC placement inhibit breastfeeding?  

Although there is theoretical concern that the progestogens in the hormonal IUS and contraceptive implant could impair the onset of lactogenesis in women receiving immediate postpartum LARC, no reduction in breastfeeding has been observed in randomized trials. Women considering immediate postpartum hormonal LARC should be counseled about the theoretical risk of reduction in breastfeeding, but that the preponderance of the evidence has not shown a negative effect on actual breastfeeding outcomes.

What is “early postpartum” LARC placement?  

Early postpartum LARC placement is defined as LARC insertion shortly after hospital discharge and within the first few weeks postpartum. The expulsion rate for early postpartum LARC placement is consistent with that for interval insertion and lower than that for immediate postpartum placement. In environments where immediate inpatient placement of postpartum LARC is not possible, a program of early postpartum placement has similar benefits and could provide similar reductions in unplanned and close-interval pregnancy. 

What is the maternal-fetal medicine (MFM) subspecialist’s role in implementing immediate postpartum LARC programs?    

MFM subspecialists are uniquely positioned to promote immediate postpartum LARC placement because of their frequent and in-depth contact with high-risk and medically complex women during pregnancy and the postpartum period. Pregnancy is a time of high motivation for contraception; this is especially true for women with complicated pregnancies who are receiving regular counseling about the maternal and fetal risks to their current and future pregnancies. Obstetric care providers can also advocate for their patients on both an individual and system-wide level.

How should patients be counseled about immediate postpartum LARC?  

Counseling should be patient-centered and provided in a shared decision-making framework, should avoid coercion, and should include the option for sterilization as well as short-acting methods. This is particularly important for low-income women and women of color, who may be more susceptible to coercion and reproductive injustice. For women who want a future pregnancy, LARC should be encouraged as an option because of its superior efficacy and longer therapeutic window. It is important to explain IUD expulsion rates and to have a plan for contraceptive management, should expulsion occur.
	
	Anticipatory guidance about side effects such as vaginal bleeding can also be provided. Obstetric care providers can use their familiarity with their patients’ health histories to help patients choose a contraceptive method that is compatible with their medical restrictions. Evidence-based contraceptive educational tools can be used by providers to assist in counseling women. 

What are the barriers to immediate postpartum LARC placement?  

Health-care system issues are the primary barrier to widespread immediate postpartum LARC use. Coordinated programs involving cooperation among providers, administration, billing, and pharmacy services are not widespread. In some religiously affiliated hospitals, immediate postpartum LARC placement may be specifically prohibited. Lack of awareness or misperceptions among MFM subspecialists and general obstetricians can impede immediate postpartum LARC placement. Insurance coverage and payment difficulties are persistent obstacles to implementation of immediate postpartum LARC placement programs and are often the result of misinformation regarding LARC clinical effects. Although Medicaid reimbursement for LARC is increasing, inpatient billing processes remain unclear for many hospitals and are not well aligned with systems for absorbing the up-front cost of the devices. Insurance coverage of IUD reinsertion in cases of postpartum expulsion and access to and coverage for removal services are also concerns for both women and obstetric care providers.

What steps can be used to increase access to immediate postpartum LARC?  

Obstetric care providers can encourage development of dedicated LARC placement teams to facilitate LARC access in both inpatient and outpatient settings. Dedicated LARC placement teams can counsel women and place LARC, provide estimates of demand and inventory stocking needs, and appropriately bill for services. Expanding the range of health care professionals, such as nurses or midwives, who are trained to counsel women and to insert LARC devices could reduce the burden on physicians. ACOG’s 

Postpartum Contraceptive Access Initiative

 provides technical assistance, resources, and free onsite training to support dedicated LARC placement teams. 

Obstetric care providers can advocate for their patients on both an individual and system-wide level. Support from MFM subspecialists and family planning experts could encourage hospital systems to develop guidelines for integrating immediate postpartum LARC into best practices that provide a policy framework for these services. Educating hospital administration about the safety, acceptability, and cost-effectiveness of immediate postpartum LARC can improve the likelihood of institutional support for a placement program. 

Counseling high-risk women about postpartum contraceptive options may not be prioritized during management of a complicated pregnancy. LARC and other postpartum contraceptive methods may not be addressed because of lack of knowledge, lack of time, or the perception by referring or MFM subspecialist providers that it is not their role. However, discussing postpartum contraceptive options early and often can increase awareness of the role of immediate postpartum contraception in improving health outcomes and reducing unplanned and close-interval pregnancy. 

This summary of SMFM Consult Series #48 provides answers to 15 frequently asked questions about postpartum contraception.  

Immediate postpartum LARC for women at high risk for medical complications

Maternal sepsis is a significant cause of maternal morbidity and mortality. Recent US data report that maternal sepsis complicates 4 to 10 per 10,000 live births. Incidence of maternal sepsis appears to be increasing; in the United States between 1998 and 2008, rates of severe maternal sepsis and sepsis-related deaths increased 10% per year. Nulliparity, black race, and public or no insurance have been identified as risk factors for pregnancy-associated sepsis. Obstetric risk factors include cesarean delivery, use of assisted reproductive technologies, and multiple gestation. More than 50% of the women who die from sepsis have one or more chronic comorbid conditions, including chronic renal disease, chronic liver disease, and congestive heart failure. 

How is sepsis defined and what are the clinical features? 

In 2016, The Third Internal Consensus Definitions for Sepsis and Septic Shock task force defined sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection.” Organ dysfunction may be objectively defined as an acute increase of two or more points in the Sequential Organ Failure Assessment (SOFA) score. Septic shock can be identified within a clinical construct of sepsis with persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mm Hg and a serum lactate level > 2 mmol/L despite adequate volume resuscitation.

A brief bedside assessment tool known as the quick SOFA score (qSOFA) can be used to assist in evaluation of suspected sepsis. The qSOFA score evaluates presence of three clinical criteria: systolic blood pressure ≤ 100 mm Hg, respiratory rate ≥ 22/min, and altered mental status. If two or more of these criteria are present, the patient is at increased risk for poor-sepsis related outcomes. These signs should prompt the physician to look carefully for organ dysfunction, start or escalate therapy, increase the acuity of monitoring, and consider transfer to an intensive care unit. Importantly, fever is neither necessary nor sufficient to determine whether sepsis is present. 

Sepsis results from a dysregulated host response to infection resulting in organ damage, and virtually any organ system can be affected. The excessive inflammatory response that occurs with sepsis includes extravasation of albumin and fluid, with resultant intravascular hypovolemia. Cytokine release leads to decreased systemic vascular resistance and increased cardiac output, although up to 60% of patients with sepsis have an ejection fraction below 45% (systolic dysfunction). Septic cardiomyopathy may also manifest with diastolic dysfunction due to cardiac edema and diminished compliance. The noncompliant left ventricle will result in decreased diastolic filling and less stroke volume, increasing risk of pulmonary edema with excessive fluid resuscitation. Tissue ischemia (and dysfunction) results not only from hypotension but also secondary to microvasculature occlusion from microthrombi due to disseminated intravascular coagulation. 

How do clinical features of sepsis differ in pregnancy?  

Normal human pregnancy is a state of expanded plasma volume, increased cardiac output, and peripheral vasodilation. None of the existing definitions of sepsis account for physiologic alterations of normal pregnancy. When nonpregnant norms are used, either overdiagnosis or underdiagnosis of sepsis may occur. Of the SOFA criteria, those most affected by pregnancy are creatinine and MAP. An obstetric-modified qSOFA has been proposed by the Society of Obstetric Medicine Australia and New Zealand (SOMANZ) and includes systolic blood pressure ≤ 90 mm Hg, respiratory rate > 25/min, and altered mental status. The SOMANZ guidelines also include modifications to laboratory components when applying the SOFA score to pregnancy, including a point value above zero for a creatinine > 90 µmol/L (1.02 mg/dL).

Most important in optimizing outcomes is early recognition of organ dysfunction in the septic patient. In addition to the SOMANZ guidelines described above, there have been other attempts to devise a pregnancy-specific scoring system for sepsis. Evaluation of the “Sepsis in Obstetrics Score,” a combination of maternal temperature, blood pressure, heart rate, respiratory rate, peripheral oxygen saturation, white blood cell count, and lactic acid level as predictors of intensive care unit (ICU) admission for sepsis and modified to account for normal physiologic changes of pregnancy reported a positive predictive value (PPV) of only 16.7% for ICU admission. A prospective validation study of the Sepsis in Obstetrics Score found that a score of 6 or greater had a sensitivity of 64%, specificity of 88%, PPV of 15%, and negative predictive value of 98.6%.

What are the most common infectious etiologies of sepsis?

The source of infection in puerperal sepsis can be either pelvic or nonpelvic. Antepartum cases of sepsis are most commonly nonpelvic in origin, while intrapartum and postpartum cases are more likely to have a pelvic source. In 30% of cases, no source is identified. In the UK Obstetric Surveillance System, clinical laboratory testing was only able to identify the causative microorganism in 64% of maternal sepsis cases, and the clinician could identify the source in only 74%. In 16%, neither the inciting organism nor the source of sepsis was identified. 

The most frequently isolated organisms in maternal sepsis are Escherichia coli and group A and group B 

, although staphylococci, gram-negative and anaerobic bacteria, and many other organisms have been reported. Mixed infections are also possible; in 15% of maternal sepsis deaths in which organisms could be identified, the infection was polymicrobial. Empiric antibiotic choices will be driven by the presumed source, likely microorganisms, and local patterns of antibiotic resistance and should include coverage of anaerobic and aerobic gram-positive and gram-negative bacteria. Hospitals may have specific recommendations in place or guidance may be sought from a consultant in infectious disease or from specialty society guidelines. Antibiotic coverage should be narrowed and focused once culture results are available.

Molecular techniques, such as polymerase chain reaction (PCR)-based systems, can identify inciting organisms not detected by culture-based methods and can provide pathogen identification from blood samples before cultures become positive. PCR testing results are positive in approximately 11% of patients with a clinical suspicion of bacteremia but negative blood cultures. 

 What is initial management of sepsis?   

Imaging is often required when searching for a source of infection. If a specific focus is identified, appropriate steps should be undertaken, such as curettage for retained products of conception or drainage of an abscess. The intervention with the least potential for physiologic derangement should be employed except in cases of necrotizing soft tissue infections, where extensive debridement is required.

What is the role of fluid therapy in sepsis management?   

Fluid resuscitation should be part of the initial intervention if hypotension or hypoperfusion is present. Fever, venodilation, and capillary leakage all lead to inadequate preload in the patient with sepsis. The Surviving Sepsis Campaign’s recommendation of an initial bolus of 30 mL/kg of crystalloid may be overly aggressive in pregnancy, where colloid oncotic pressure is lower and risk of pulmonary edema is higher. Patients who are fluid responsive should be identified before further fluid administration (especially after the initial 1 to 2 liters, or 30 mL/kg, have been administered) by dynamic measures of preload. For pregnant women, these include analysis of pulse-pressure variation in the waveform of an arterial line and passive leg raising. The former method is only reliable in sedated individuals receiving positive-pressure, controlled mechanical ventilation and who are in sinus rhythm. A pulse-pressure variation of more than 13% with the respiratory cycle identifies the patient as volume responsive. 

For patients who are breathing spontaneously and in sinus rhythm, passively raising the legs 30 to 45 degrees causes an autotransfusion of close to 300 mL of blood from the legs into the chest. After 2 to 3 minutes of passive leg raising, fluid responders will have an increase in cardiac output (utilizing noninvasive cardiac output monitors), while those who do not improve are probably better treated with vasopressors. Passive leg raising may not be useful during the third trimester due to uterine compression of the inferior vena cava and should not be used to guide therapy. In such cases, an increase in cardiac output may be identified by administering a small bolus of fluid (250-500 cc); if cardiac output increases after such an intervention, further fluid administration is likely indicated. Determination of fluid responsiveness using point-of-care ultrasound measurements of the diameter of the inferior vena cava with respiration is most commonly used in patients receiving mechanical ventilation and has not been validated in pregnancy.

 When are vasopressors and inotropes indicated?   

In hypotensive patients who are not fluid responsive or who are not candidates for further fluid resuscitation (e.g., women who are in pulmonary edema), vasopressors should be utilized to increase blood pressure. The purpose of vasopressors is to constrict the pathologically dilated systemic circulation and maintain adequate perfusion. Current guidelines recommend norepinephrine as the first-line agent with a target MAP above 65 mm Hg, although the latter threshold has not been studied in pregnant women. Determining the target MAP in a septic pregnant patient must be individualized, with consideration of overall organ perfusion. Lower blood pressures may be acceptable during pregnancy provided no signs of hypoperfusion are present (such as altered mental status, oliguria, elevated serum lactate, cold extremities, or evidence of fetal compromise). Early goal-directed therapy is no longer recommended in management of sepsis.

Norepinephrine has been studied in human pregnancy and is often used to maintain blood pressure with regional anesthesia at time of cesarean delivery. Norepinephrine appears to be safe for the fetus, especially at low doses.

When is delivery indicated in pregnant women with sepsis?   

Presence of sepsis alone is not an immediate indication for delivery (except in cases of chorioamnionitis). Delivery should be reserved for the usual obstetric indications after stabilization of the woman; there is no evidence that delivery improves maternal outcomes. The primary objective should be hemodynamic supportive therapy for maternal benefit and antimicrobial treatment with appropriate source control of the infection. Corticosteroids for fetal lung maturity are not contraindicated and may be used in sepsis if indicated (regardless of use of hydrocortisone for refractory septic shock). Norepinephrine has been studied in human pregnancy and is often used to maintain blood pressure with regional anesthesia at time of cesarean delivery. Norepinephrine appears to be safe for the fetus, especially at low doses.

What are the maternal and perinatal outcomes associated with sepsis?   

The mortality rate for sepsis in pregnant women is difficult to quantify. The few existing studies have reported rates from 1% to 4.6%. Because incidence of and mortality from sepsis are dependent on age, comparisons to the general population depend on finding a similar group of reproductive-age women. In 2012, an analysis from New Zealand and Australia found the mortality rate in young adults aged 44 years and younger to be 8% in the absence of comorbidities. 

Preterm delivery is common after critical maternal illness, including sepsis, even when the source is not uterine. An Irish study found that in women with antepartum bacteremia, 69% either miscarried or delivered preterm. The outcome was worse for women with antepartum bacteremia of uterine origin; all delivered within 24 hours of onset. Among women with a nonpelvic source of bacteremia in the antepartum period, 12% miscarried, 33% delivered soon after onset, and the remainder delivered between 1 week and 7 months after onset.

How can deaths from sepsis be prevented?  

Among women who died from sepsis, a majority had a delay in care and a delay in escalation of care. Most were afebrile, possibly delaying recognition of presence of sepsis. Even after diagnosis, 73% of women were started on antibiotics that provided inadequate coverage. Implementation of an early warning system may decrease maternal risk. In addition, with publication of the Surviving Sepsis guidelines, early involvement of consultants with expertise in infectious disease may expedite treatment of sepsis and help improve outcomes. 

Incidence of maternal sepsis appears to be increasing. Here's what ob/gyns need to know about identification and treatment.

Publications Committee

Articles

SMFM Consult Series #60: Management of pregnancies resulting from IVF

Immediate postpartum LARC for women at high risk for medical complications

Sepsis during pregnancy and the puerperium