Care plans for women pregnant using assisted reproductive technologies: a systematic review

Advances in infertility treatments have helped many couples to achieve a pregnancy. Some of these pregnancies may have a higher risk of complications for the mothers and the babies. The cause of infertility, the type of treatment, or both could play a role in these adverse events. Despite previous advances in the care of women who are expecting, there are few clinical practice guidelines specific to pregnant women who conceive with infertility treatment. Thus, we conducted a systematic review of current clinical practice guidelines to identify gaps in knowledge, including recommendations for clinical care and optimal maternity care provider and setting for women who conceived following infertility treatments. Only 10 guidelines were identified, and the quality of the evidence varied, with only one guideline considered of high quality. They recommend that antenatal care for these pregnancies should be provided by specialist with knowledge in obstetrics. In the case of a higher order multiple pregnancy, the parents should receive information about the risk/benefits of selective pregnancy reduction. Since some advanced infertility treatments may be associated with congenital abnormalities, prenatal genetic screening should be offered. The treatment of thromboembolic diseases and thyroid problems should be the same as for pregnancies conceived spontaneously. Finally, the stress associated with these pregnancies is recognized, and as such psychosocial support should be provided. We conclude that there is a lack of specific guidelines for pregnant women following infertility treatment, and new guidelines should be developed to decrease complications during pregnancy for this population.

Infertility has been declared as an emerging public health priority in developed countries [1]. It is estimated that 10–15% of couples experience infertility, which is defined as a failure to conceive after 12 months of unprotected intercourse [2]. Assisted reproductive technologies (ART) are used to assist couples attempting to overcome the challenge of infertility. Between 1 and 5% of children in industrialized countries are conceived through ART [3], and this number is expected to increase further as more countries provide access as part of their healthcare system [4].

Some studies suggest that ART pregnancies are associated with adverse maternal and perinatal outcomes, including preeclampsia, placenta previa, caesarean delivery, preterm birth, low birth weight, and congenital malformations, even among singleton pregnancies [5‐7]. The reasons for this higher risk relate to both the underlying cause of infertility and the ART itself [8, 9]. Within the continuum of reproductive health care, antenatal care (ANC) aims to optimize maternal and perinatal outcomes through health promotion, screening and diagnosis, and disease prevention [10]. Currently, there are few clinical practice guidelines (CPGs) that address either the setting where ANC should be provided to pregnant women following ART or specific recommendations to be implemented with the aim to decrease adverse outcomes. Typically, couples are discharged from the fertility clinic to receive standard ANC, but there is currently little evidence to support whether this care adequately meets the need of ART pregnancies [11].

The objective of this systematic review was to identify the recommended care plans for women becoming pregnant with ART which are currently discussed in existing CPGs. This review focuses upon care given to women pregnant with the involvement of ART during pregnancy and delivery.

This review has been reported with guidance from the PRISMA reporting guideline [12] and followed an a priori protocol, which was registered in PROSPERO (PROSPERO # CRD42017073228) and posted publicly in the University of Ottawa Library’s online repository (http://​hdl.​handle.​net/​10393/​36555).

Few existing CPGs for women pregnant following ART were identified. A total of 10 guidelines were included, with a focus on models of care, risks of ART, screening in pregnant women, care of women with conditions not specific to those pregnant using ART, and psychosocial counselling for those involved in ART. The associated degree of rigor based on formal quality assessments using the AGREE-II tool was found to be both variable and limited; only one CPG, the ESHRE guideline, referenced a full publication [32], which provided additional information on several key considerations (methodology, the process of external review, and information for updating) which led to a notably higher score. Efforts should be made to improve the quality of future guidelines since rigorously developed CPGs have shown to improve healthcare processes and patient outcomes [42].

Recommendations within these guidelines related to the population were often based on observational studies and expert opinion. Many of the recommendations were indicated to be the same as for the care suggested for women who conceive spontaneously. This was either due to a lack of evidence specific to women who conceived with ART, conflicting evidence, or because the evidence suggested that there was little or no difference between these women. Additionally, the recommendations from the ACCP CPG were based on some evidence on women who were undergoing ART treatment and not yet pregnant, however, this evidence was combined with studies that included women who were followed through pregnancy.

Several fundamental points of care can be drawn from the CPGs that were reviewed. One of the main differences of care for women becoming pregnant using ART (relative to those conceiving spontaneously) was for those who became pregnant with IVF-ICSI, because of a higher risk of birth defects [34, 35]. In these cases, prenatal diagnosis screening is recommended [43]. Of note, none of the guidelines discussed about Prenatal Genetic Screening/Prenatal Genetic Diagnosis (PGS/PGD) and perinatal outcomes, a more recent technology that needs to be addressed in future CPGs. In addition, there is sufficient evidence that multi-fetal pregnancies (triplets or more) contribute to high risk pregnancies, deliveries, and poorer outcomes [44, 45]. These pregnancies should be avoided, and if they occur, the option of selective reduction should be discussed, including the emotions associated with this and the possibility of loss of the entire pregnancy [46]. A common theme throughout many of the guidelines was the need for counselling prior to treatment, during treatment, and during pregnancy. Many of the decisions that are to be made in the course of ART treatment should be discussed with qualified health professionals, including the risks associated with treatment (e.g. multi-fetal pregnancies) [45], risks during pregnancy (e.g., preeclampsia) [47], higher risk deliveries (e.g., postpartum hemorrhage) [48], and risk to the baby (e.g., low birth weight, pre-term delivery) [49]. It should be noted that not all ART methods were addressed in the set of included CPGs (e.g., no specific mention for surrogate mothers). There may be a need to consider different care options depending on the different types of ART, as some techniques are associated with additional risks. For example, some evidence indicates that there is an increased risk of preeclampsia with IVF but not for IUI compared to spontaneous conception [47]. Others have reported a higher risk of preeclampsia in women conceiving by IUI with donor sperm compared with partner sperm [50]. Comparing pregnancies with donor oocytes to autologous IVF, there is an increased risk for pregnancy-induced hypertension [51] and preeclampsia [52].

Important gaps were noticed. Clear indications for directing women pregnant using ART to low- versus high-risk antenatal care do not exist. Furthermore, consensus regarding ideal antenatal care (including details such as types and timing of screening tests, medication and supplement dosing and timing of delivery) of these women is lacking in both low-risk and high-risk settings. Although it is recognized that there is a higher incidence of mono-chorionic twinning with IVF than the general population, none of the guidelines addressed the use of early ultrasound to determine twin chorionicity. In relation to evidence-base recommendations known to decrease adverse pregnancy outcomes in women at high risk, none of the identified CPGs considered folic acid supplementation to decrease the risk of congenital anomalies in ART pregnancies, or the use of low-dose aspirin to decrease the risk of preeclampsia. Moreover, recent guidelines specific to these two recommendations in the general obstetrical population, did not identify ART pregnancies as a high risk population who could benefit from an adjusted dose of folic acid [53], or low-dose aspirin after 12 weeks of gestation [54]. Finally, we did not identify guidelines addressing interventions during delivery (e.g. induction of labor versus spontaneous labor onset, cesarean section versus vaginal delivery) in pregnancies conceived through ART.

There is evidence that supports an increased risk of adverse maternal and perinatal outcomes in pregnancies conceived using ART. The underlying cause of infertility may play a role, and even within ART, there appears to be different levels of risk depending on the technology used. As this quality of evidence grows and improves, CPGs specific to this population need to be re-evaluated. Although the quality of most included guidelines were deemed to require modifications (e.g., provide additional details of methodology), it is recommended that women who conceive using ART should be followed by health care providers with a recognized postgraduate qualification in obstetrics, be offered appropriate screening and diagnostic tests, and have access to psychosocial counselling throughout the entire process. The benefit of current recommendations known to decrease the risk of congenital malformations and preeclampsia in the general obstetrical population should be evaluated in ART pregnancies.