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Care plans for women pregnant using assisted reproductive technologies: a systematic review
Reproductive Healthvolume 16, Article number: 9 (2019)
Between 1 and 5% of children in industrialized countries are conceived through Assisted Reproductive Technologies (ART). As infertility and the use of ART may be associated with adverse perinatal outcomes, care plans specific to these pregnancies are needed. We conducted a systematic review to examine the existing care plans specific to women pregnant following Assisted Reproductive Technologies (ART).
MEDLINE, Embase and the Cochrane Library were searched by a senior information specialist. The population of interest included women becoming pregnant with ART (e.g., Intra-Uterine Insemination, In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), and surrogacy). All proposed care plans were sought that pertained to any aspect of care during pregnancy and delivery. Only Clinical Practice Guidelines (CPGs) addressing the recommendations and plans for the care of ART pregnant women were included. The search was restricted to the publication dates 2007 to June 12, 2017 when the search was run. The search was not restricted by language, however only English and French language guidelines were considered for inclusion.
After screening 2078 citations, a total of ten CPGs were included. The following key clinical messages were prevalent: (1) although there was no supporting evidence, antenatal care for ART pregnancies should be provided by specialist with knowledge in obstetrics; (2) high-order multiple pregnancies are the greatest risk of ART and selective reduction options should be discussed; (3) there is some evidence of increased risk of congenital abnormalities and prenatal genetic and anatomic screening is recommended, especially in IVF-ICSI pregnancies; (4) due to a lack of or conflicting evidence, treatment of venous thromboembolism, antithrombotic therapy, treatment for hypothyroidism, and women with positive thyroid antibodies is recommended to be the same as in spontaneous pregnancies; and lastly (5) since an increased level of distress is a recognized feature in these pregnancies, psychosocial care and counselling should be considered.
There is a lack of CPGs specific to ART pregnancies. While we identified a small number of recommendations for ART pregnancies, specific interventions and models of care aiming at decreasing adverse maternal and perinatal outcomes following ART should be developed, implemented, and evaluated.
Plain English summary
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 . It is estimated that 10–15% of couples experience infertility, which is defined as a failure to conceive after 12 months of unprotected intercourse . 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 , and this number is expected to increase further as more countries provide access as part of their healthcare system .
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 [5,6,7]. 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 . 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 .
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  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).
Criteria to identify eligible publications for the current review were established using the PICOS (Population-Intervention-Comparators-Outcomes-Study design) framework.
The population of interest included women becoming pregnant with involvement of ART (e.g., Intra-Uterine Insemination (IUI), In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), and surrogacy).
All proposed care plans were sought that pertained to any aspect of care for these women during pregnancy and delivery. This included women in both low risk (e.g., care from a general practitioner or midwife) and high risk settings (e.g., care from an obstetrician or maternal-fetal medicine).
Areas of interest
Any CPGs addressing the recommendations and plans for the care of ART pregnant women were included. Information of interest included the following: recommendations related to different types of maternity care providers (e.g., obstetrician, general practitioner, and midwife) and location of care (e.g., clinic, hospital); details of the care plans and/or individual elements recommended (e.g., including (but not limited to) the number and types of ultrasounds during pregnancy, prenatal screening, and so forth); underlying evidence supporting the recommendation (e.g., systematic reviews; if available, details on the approach to generate evidence for recommendations); citations of studies cited as informing the recommended care plans.
Only CPGs were included. Primary studies, abstracts, letters, commentaries, and non-guideline reviews were excluded. There were no restrictions imposed on the setting, or geographic location. The search was not restricted by language, however only English and French language guidelines were included.
The search strategies were developed and tested through an iterative process by an experienced medical information specialist (BS) in consultation with the review team. The strategies were peer reviewed by another senior information specialist prior to execution using the PRESS Checklist . Using the OVID platform, we searched Ovid MEDLINE®, including Epub Ahead of Print and In-Process & Other Non-Indexed Citations, and Embase. We also undertook a grey literature search of guideline registries listed in CADTH’s Grey Matters: a practical tool for search health-related grey literature (https://www.cadth.ca/resources/finding-evidence/grey-matters) and targeted specialty societies. All searches were undertaken on June 12, 2017.
Strategies utilized a combination of controlled vocabulary (e.g., “Prenatal Care”, “Reproductive Techniques, Assisted”, “Clinical Protocols”) and keywords (e.g., “antenatal”, “ART”, “pathway”). A guidelines/care pathway filter was applied and vocabulary and syntax were adjusted across the two databases. The search was restricted to the publication dates 2007 to the present. Animal-only, opinion pieces and conference abstracts were removed from the results.
Specific details regarding the strategies appear in Additional file 1.
Data collection and analyses
Search results were de-duplicated in Reference Manager  before uploading to Distiller Systematic Review Software® . Screening was performed in two stages: title/abstract screening and full text screening. Screening questions were developed and pilot-tested on a subset of records before implementation (50 references for title and abstract screening and 10 for full-text screening). All titles and abstracts were screened in duplicate by two independent reviewers, using the liberal accelerated method . This method requires only one reviewer to assess an abstract as eligible for full text screening, and requires two reviewers to deem the abstract irrelevant. Full text articles for references included based on title and/or abstract were retrieved and assessed for inclusion at full-text screening, by two independent reviewers. Discrepancies were resolved by consensus. The process of study selection is reported below using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram , including reasons for excluding full-text articles.
References that did not contain an abstract were screened based on the title, and those determined to be clearly not relevant were excluded. If there was any indication that the title may be relevant, or it was unclear, it was passed through to full-text screening
Data extraction forms were developed in Microsoft Excel 2007 and pilot tested on one included guideline. One reviewer extracted all data and a second reviewer verified all of the information collected. For all included CPGs, the following study characteristics were extracted: authorship list; guideline funders and sponsoring society; CPG type (new versus update of an existing CPG); date of publication; journal of publication/website; and country/language of publication. Other guideline information that were extracted included the following clinical details: recommendations related to different types of maternity care providers (e.g., obstetricians, general practitioners, midwife), location of care (e.g., clinic, hospital); details of the care plans and/or individual elements recommended (e.g., prenatal screening); underlying evidence (e.g., systematic reviews; if available, details on the approach to generate evidence for recommendations was collected); citations of studies cited as informing the recommended care plans.
Quality assessment was performed on each clinical research guideline using the Appraisal of Guidelines for Research & Evaluation (AGREE)-II tool . This tool consists of six domains as follows: (1) scope and purpose, which addresses the overall objectives of the guideline, if the health questions are specifically described and if the population to whom the guideline is meant to apply is well described; (2) stakeholder involvement, which addresses who was involved in the development of the guideline, if the views and preferences of the target population have been sought, and if the target users are clearly defined; (3) rigor of development, which addresses the methodological quality of the guideline, including clear reporting of the criteria for inclusion, the strengths and limitations of the evidence, the methods for formulating the recommendations, external review of the guideline and a process for updating; (4) clarity of presentation, which addresses how well the recommendations are presented; (5) applicability, which addresses how well the guideline provides guidance on the implementation, barriers and facilitators to its application; and (6) editorial independence, which addresses the how the source of funding may have influence the content and any competing interests of the guideline development group.
For the current review, the checklist was implemented in DSR, and three reviewers independently assessed the quality of each included guideline using this checklist. Three reviewers were used to increase the validity of the overall findings, as suggested by the AGREE-II Next Steps Consortium . For any question where there was a difference greater than two points in the assessment between all reviewers, the discrepancy was discussed and consensus was reached. Each domain score was calculated as described in the AGREE-II user’s manual . As the Consortium has not set minimum domain scores or patterns of scores across domains to differentiate between high quality or poor quality guidelines, an overall quality score of 1–3 was considered low quality. An overall quality score of 4–5 was considered moderate quality. Lastly, a score of 6–7 was considered high quality. A narrative description of the quality assessment findings is presented, identifying domains of highest and lowest scores amongst the CPGs included in the review.
Recommendations from the included CPGs were summarized narratively according to the category of recommendations, which were chosen to be (1) models of care; (2) risks of ART; (3) surveillance, screening, and diagnostic testing in pregnancy; (4) treating conditions in pregnancy; and lastly (5) psychosocial care and counseling. Within each of these categories, we summarized recommendations described by at least one of the included CPGs, summarized the number of CPGs stating these recommendations, and indicated the assigned grade of evidence (where available). Within each of the categories of care, recommendations related to sub-aspects of care were grouped and contrasted where differences in recommendations were identified.
The search across databases produced a total of 2173 records. After de-duplication and adding the records identified from the grey literature search and bibliographic screening of the included guidelines, 2078 unique records were assessed based on title and abstract. A total of 138 records were evaluated at full-text, and 10 guidelines were included (Fig. 1). Table 1 provides an overview of the primary characteristics of the included CPGs. [18,19,20,21,22,23,24,25,26,27]. Additional file 2 provides a list of studies that were excluded during full-text screening, with reasons.
Characteristics of included studies
Ten guidelines provided several recommendations for women who became pregnant using ART, although not all were specifically written to address only these pregnancies. Eight CPGs were published in 2012–2017 [18, 21,22,23,24,25,26,27] with two older CPGs published in 2009  and 2011 . Three CPGs were published from the Society of Obstetricians and Gynaecologists of Canada (SOGC), and all were updates that replaced older guidelines for the same topic. These guidelines focused on pregnancy outcomes after ART , venous thromboembolism and antithrombotic therapy in pregnancy , and prenatal screening for fetal aneuploidy in singleton pregnancies . Two guidelines focused on psychosocial counseling specifically for gamete donation  and the fertility staff involved with medically assisted reproduction . These were published by the German Infertility Counselling Network, and the European Society of Human Reproduction and Embryology (ESHRE), respectively. One guideline addressed maternal suitability for models of care from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) . One guideline addressed perinatal risks associated with ART from the American College of Obstetricians and Gynecologists (ACOG) . Lastly, two CPGs addressed care to women during pregnancy with thyroid disorders [23, 24].
Six CPGs did not state how the development of the guideline was funded [18,19,20, 24,25,26]. The four CPGs that provided funding information were funded by the ESHRE , the RANZCOG , the American Thyroid Association , and the American College of Chest Physicians (ACCP) . A total of five (50%) clearly indicated that recommendations were based upon systematic reviews of the evidence, and seven (70%) assigned formal grading of the recommendations; three CPGs [18, 19, 26] citing the Canadian Task Force on Preventive Health Care , one CPG  citing the Scottish Intercollegiate Guidelines Network , one CPG  citing Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) , and one CPG  citing the American College of Physicians Grading System . One CPG  used and described a grading system, but did not formally reference the system.
Quality of the guidelines
Overall, the quality of the published guidelines varied, with three CPGs considered low quality, six considered moderate quality and one CPG developed from the ESHRE considered high quality , as it provided a link to the full CPG , which was assessed. Questions typically did not score well due to a lack of reporting, either by complete omission of the information, or from not including enough of the criteria as suggested by the AGREE-II user’s manual. A narrative description of each domain is provided next, while overall scoring of each domain is provided in Table 2.
Regarding the scope and purpose domain, scores ranged from 22 to 100% (median 72%). CPGs that scored low in this domain did not provide sufficient information on the target population of interest or a clear description of the health questions covered by the guideline.
With respect to the stakeholder involvement domain, scores ranged from 13 to 87% (median 29%). Guidelines typically specified the names and geographic location of the development group, but failed to specify discipline or content expertise, their institution, or a description of the member’s role in the guideline development group. Only one guideline  specifically sought the views and preferences of the target population and incorporated these perspectives into the guideline and its recommendations.
Concerning the rigour of development domain, scores ranged from 3 to 85% (median 40%). Excluding the CPG by the ESHRE, the range was 3 to 59%. In general CPGs were associated with a lack of reporting of several key details including (i) the methodology used for study selection; (ii) the methods used to formulate recommendations; (iii) the approach to how the external review was performed; and (iv) a description of the procedure for updating the guideline. None of the included CPGs provided the literature search strategies used or a link to the search strategies used.
In regard to the clarity of presentation domain, scores ranged from 17 to 89% (median 78%). One guideline received a low score ; after excluding it, scores ranged from 57 to 89%. Recommendations were specific, easily understood and identifiable, either by bullet points, numbered, or presented in greyed-out boxes.
With respect to the applicability domain, scores ranged from 6 to 57% (median 7%; range 6 to 17% without the ESHRE guideline) . Overall, there was little or no information on advice on how to use the guideline in practice, the facilitators and barriers to its application, the potential resource implications of applying the recommendations, and the monitoring or auditing criteria of the CPG.
With reference to the editorial independence domain, scores ranged from 0 to 97% (median 4%). Funding information was not provided in most CPGs, and aside from generic statements that “disclosure statements have been received from all contributors”, there was no further information about any competing interests of the CPG development group members.
Results of included guidelines
Narrative summaries with table-based presentations (Tables 1 and 3) are provided to summarize proposed aspects of care plans identified from the included literature. A detailed table of all recommendations and supporting publications is presented in Table 4. Most CPGs included any method of ART and may have provided information for a sub-type of ART (e.g., IVF-ICSI), while some were specific to a certain method (e.g., only donor insemination). CPG recommendations were grouped in five categories depending on the focus of the CPG: (1) models of care; (2) risks of ART; (3) surveillance, screening and diagnostic testing during pregnancy; (4) treating conditions in pregnancy; and (5) psychosocial counselling for those involved in ART.
Models of care
One CPG reviewed the models of care in Australia and New Zealand, and referral within and between models . This guideline is not specific to women who became pregnant using ART, but provides guidance on what type of clinician should care for women who needed IVF or gamete intrafallopian transfer (GIFT) to conceive. The recommendation is that these women should be followed by a general practitioner with a recognized postgraduate qualification in obstetrics. In the case where a GP with suitable qualifications is not available, referral should be to a specialist obstetrician.
Risks of ART
The ACOG guideline discussed the perinatal risks associated with ART . Multi-fetal pregnancy (triplets or more) is more common in pregnancies achieved through ART, and its associated outcomes are the greatest risk of ART. This CPG provides a recommendation to discuss the risk and options if this occurs and makes reference to another CPG by the ACOG on multi-fetal pregnancy reductions and states: “when a patient request for multi-fetal pregnancy reduction is discordant with the physician’s value system, the patient should be referred to a physician with expertise in performing multi-fetal pregnancy reductions .”
Surveillance, screening, and diagnostic testing in pregnancy
Two SOGC guidelines discussed surveillance, screening and/or diagnostic testing for these women as there are several known risks (e.g., preeclampsia, preterm birth) associated with pregnancy achieved with ART [18, 19]. Although there was insufficient formal evidence, due to these known additional risks and/or other factors that may influence decision-making, expert opinion was considered in the recommendation that there is a need for closer surveillance during these pregnancies.
Several well-designed observational studies cited by the SOGC guidelines reported a higher prevalence of congenital malformations (Hazard Ratio (HR) 1.20; 95%CI 1.07–1.35), genital organ malformations (HR 2.32; 95%CI 1.24–4.35), and congenital defects, including septal heart defects (adjusted Odds Ratio (aOR) 2.1; 95%CI 1.1–4.0), esophageal atresia (aOR 4.5; 95%CI 1.9–10.5), and anorectal atresia (aOR 3.7; 95%CI 1.5–9.1) compared to spontaneously conceived infants [34, 35]. This suggests that an ultrasound for congenital abnormalities is recommended. The ACOG guideline also suggested that these women should be offered ultrasonographic surveillance for structural abnormalities and identified some professional organizations that recommend fetal echocardiography in all ART pregnancies, although the incremental yield is unclear .
Studies have evaluated several different maternal serum levels (e.g., Alfa fetoprotein-(AFT), Estradiol (uE3), Pregnancy associated plasma protein-A (PAPP-A), Human chorionic gonadotropin (HCG), etc) during the first and second trimesters of pregnancy. In observational studies cited by the CPG, there has been conflicting evidence that there are differences in some of these serum levels between pregnancies through IVF and non-IVF [36,37,38]. As screening programs typically collect information on IVF, it is recommended that this information is provided to the laboratory, but further investigation is necessary to determine if adjustment is necessary .
Although the incidence of chromosomal abnormalities in births and induced terminations following IVF (0.7%) has been shown to be similar to those in spontaneous conceived pregnancies (0.2%), it has been shown to be significantly higher among those who became pregnant with IVF-ICSI (1.0%) . Further supported by a SOGC guideline on prenatal screening for fetal aneuploidy in singleton pregnancies , in the case of pregnancy conceived by IVF-ICSI, the risk of chromosomal abnormality is high enough to offer invasive testing without prior non-invasive screening or based on a non-invasive screen result above the risk cut-off.
Treating conditions in pregnancy
The SOGC and ACCP CPGs focused on venous thromboembolism (VTE) and antithrombotic therapy in pregnancy and on how to diagnose and treat VTE in pregnancy and postpartum [26, 27]. One of the 67 recommendations in the SOGC CPG and two of the 37 recommendations from the ACCP CPG addressed women who became pregnant with ART and how to treat them during pregnancy. The SOGC CPG authors stated that the risk in women undergoing ART is estimated to be 0.11% per cycle of IVF (3 cases among 2748 IVF cycles) , similar to the general population of pregnant women (1 in 1000 pregnancies) . The ACCP CPG found that while ART may be a risk factor, the incidence of thrombosis in ART patients was low (0.1 and 0.3%) [39, 41]. However, the risk of thrombosis was found to be higher in women with Ovarian Hyperstimulation Syndrome (OHSS), although based on observational data (up to 4.1% (95% CI, 1.1–13.7% in severe cases) . There is little to guide clinicians in the use of thromboprophylaxis in women undergoing ART. Deriving from observational data of pregnant women (not specific to ART) at high risk for VTE (e.g. personal history of previous VTE, asymptomatic thrombophilia, family history of symptomatic thrombophilia, combined pregnancy-related risk factors) recommendations from the SOGC CPG are that thromboprophylaxis should be initiated if pregnancy is achieved. Among those with no risk factors for VTE, routine thromboprophylaxis is unnecessary. The ACCP CPG recommends against routine thromboprophylaxis for women undergoing ART. For those who develop severe OHSS, thromboprophylaxis for 3 months postresolution of the condition is suggested.
Two CPGs focused on women with thyroid disease, specifically hypothyroidism, and how it should be treated in pregnancy [23, 24]. Although both CPGs developed recommendations with the consideration of RCT and observational studies using women pregnant through ART (e.g., ovarian hyperstimulation, IVF), both CPGs recommend treating these women the same as those who conceived spontaneously. This is mainly due to the high level of conflicting evidence in these studies. Specific recommendations focus on treating TSH elevations and offering levothyroxine treatment to improve pregnancy outcomes in women with positive thyroid antibodies.
Psychosocial care and counselling
A guideline from the ESHRE  provided information for all fertility clinic staff (e.g., doctors, nurses, midwives, counselors, social workers) on when they should refer patients for additional psychosocial care after a successful pregnancy with ART treatment. No interventions were found to address behavioural, relational and social, emotional, and cognitive needs of these patients. The reviewed evidence suggested that the needs of couples who achieved pregnancy with fertility treatment did not differ from the needs of those who conceived spontaneously . As there was no existing evidence available, recommendations were based on “good practice points” informed by expert opinion. In summary, fertility staff should refer or offer additional psychosocial care to patients at increased risk of experiencing psychosocial distress or problems, or to discuss their worries about the pregnancy .
German guidelines provided information for psychosocial counseling in the area of gamete donation, specific to donor insemination, as this is the only legal form of gamete donation in Germany . There are several complexities which are associated with building a family with the assistance of donated semen which differ from building a family with gametes of both intended parents, including the differences between biological and social parenthood, how this affects the members of the intended family and any family of the donor, and how it impacts the future child. One recommendation is specific to how both partners may feel toward the donated semen and suggests that counselling can help towards understanding and managing these feelings.
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 , 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 .
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 . 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 . 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) , risks during pregnancy (e.g., preeclampsia) , higher risk deliveries (e.g., postpartum hemorrhage) , and risk to the baby (e.g., low birth weight, pre-term delivery) . 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 . Others have reported a higher risk of preeclampsia in women conceiving by IUI with donor sperm compared with partner sperm . Comparing pregnancies with donor oocytes to autologous IVF, there is an increased risk for pregnancy-induced hypertension  and preeclampsia .
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 , or low-dose aspirin after 12 weeks of gestation . 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.
American College of Chest Physicians
American College of Obstetricians and Gynecologists
Appraisal of Guidelines for Research & Evaluation
Adjusted Odds Ratio
Assisted Reproductive Technologies
Clinical Practice Guidelines
European Society of Human Reproduction and Embryology
Gamete intrafallopian transfer
Grading of Recommendations, Assessment, Development, and Evaluation
Human chorionic gonadotropin
Intracytoplasmic Sperm Injection
In Vitro Fertilization
Ovarian Hyperstimulation Syndrome
Pregnancy associated plasma protein-A
Prenatal Genetic Diagnosis
Prenatal Genetic Screening
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Society of Obstetricians and Gynaecologists of Canada
Macaluso M, Wright-Schnapp TJ, Chandra A, Johnson R, Satterwhite CL, Pulver A, et al. A public health focus on infertility prevention, detection, and management. Fertility and sterility. 2010;93(1):16 e1–0.
Buck, Louis GM. Fecundity and Fertility. In: Buck Louis GM, Platt RW, editors. Reproductive and perinatal epidemiology. Oxford New York: Oxford University Press; 2011.
Centers for Disease Control and Prevention. National Public Health Action Plan for the Detection, Prevention, and Management of Infertility. 2014.
Velez MP, Connolly MP, Kadoch IJ, Phillips S, Bissonnette F. Universal coverage of IVF pays off. Human reproduction (Oxford, England). 2014;29(6):13 13–9.
Reddy UM, Wapner RJ, Rebar RW, Tasca RJ. Infertility, assisted reproductive technology, and adverse pregnancy outcomes: executive summary of a National Institute of Child Health and Human Development workshop. Obstet Gynecol. 2007;109(4):967–77.
Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012;98(2):368–77 e1–9.
Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(5):485–503.
Messerlian C, Maclagan L, Basso O. Infertility and the risk of adverse pregnancy outcomes: a systematic review and meta-analysis. Human reproduction (Oxford, England). 2013;28(1):125–37.
Luke B, Stern JE, Hornstein MD, Kotelchuck M, Diop H, Cabral H, et al. Is the wrong question being asked in infertility research? J Assist Reprod Genet. 2016;33(1):3–8.
World Health Organization. WHO recommendations on antenatal care for a positive pregnancy experience. 2016.
Darwiche J, Maillard F, Germond M, Favez N, Lancastle D, de Roten Y, et al. The transition of care from fertility specialists to obstetricians: maternal adjustment and postpartum depressive symptoms. Women's health (London, England). 2013;9(1):109–18.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9 w64.
McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS peer review of electronic search strategies: 2015 guideline statement. J Clin Epidemiol. 2016;75:40–6.
Thomson Reuters. Reference manager 12 [computer program]. New York: Thomson Reuters; 2011.
Evidence Partners: DistillerSR [computer program]. Ottawa: Evidence Partners. 2011.
Khangura S, Konnyu K, Cushman R, Grimshaw J, Moher D. Evidence summaries: the evolution of a rapid review approach. Syst Rev. 2012;1:10.
Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010;182(18):E839–42.
Okun N, Sierra S. Genetics committee. Pregnancy outcomes after assisted human reproduction. J Obstet Gynaecol Can. 2014;36(1):64–83.
Chitayat D, Langlois S, Douglas Wilson R. SOGC Genetics committee. Prenatal screening for fetal aneuploidy in singleton pregnancies. J Obstet Gynaecol Can. 2011;33(7):736–50.
Thorn P, Wischmann T. German guidelines for psychosocial counselling in the area of gamete donation. Human fertility (Cambridge, England). 2009;12(2):73–80.
Gameiro S, Boivin J, Dancet E, de Klerk C, Emery M, Lewis-Jones C, et al. ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction-a guide for fertility staff. Human reproduction (Oxford, England). 2015;30(11):2476–85.
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Maternal suitability for models of care, and indications for referral within and between models of care. 2015.
Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and Management of Thyroid Disease during Pregnancy and the postpartum. Thyroid. 2017;27(3):315–89.
American Society for Reproductive Medicine. Subclinical hypothyroidism in the infertile female population: a guideline. Fertil Steril. 2015;104(3):545–53.
American College of Obstetricians and Gynecologists. Committee opinion no 671: perinatal risks associated with assisted reproductive technology. Obstet Gynecol. 2016;128(3):e61–8.
Chan WS, Rey E, Kent NE, Corbett T, David M, Douglas MJ, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can. 2014;36(6):527–53.
Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e691S–736S.
Woolf SH, Battista RN, Angerson GM, Logan AG, W. E. Canadian Task Force on Preventive Health Care. New grades for recommendations from the Canadian Task Force on Preventive Helath Care. CMAJ. 2003;169:207–8 2003.
Scottish Intercollegiate Guidelines Network EH -HC, Edinburgh EH7 5EA. http://www.sign.ac.uk. (Accessed 23, Aug 2017),. 2001–2013.
Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ (Clinical research ed). 2004;328(7454):1490.
Qaseem A, Snow V, Owens DK, Shekelle P. The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods. Ann Intern Med. 2010;153(3):194–9.
ESHRE Psychology and Counselling Guideline Development Group. Routine psychosocial care in infertility and medically assisted reproduction – a guide for fertility staff2015 august 11, 2017.
American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 553: multifetal pregnancy reduction. Obstet Gynecol. 2013;121(2 Pt 1):405–10.
Reefhuis J, Honein MA, Schieve LA, Correa A, Hobbs CA, Rasmussen SA. Assisted reproductive technology and major structural birth defects in the United States. Human reproduction (Oxford, England). 2009;24(2):360–6.
Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ (Clinical research ed). 2006;333(7570):679.
Wald NJ, White N, Morris JK, Huttly WJ, Canick JA. Serum markers for Down's syndrome in women who have had in vitro fertilisation: implications for antenatal screening. Br J Obstet Gynaecol. 1999;106(12):1304–6.
Maymon R, Shulman A. Serial first- and second-trimester Down's syndrome screening tests among IVF-versus naturally-conceived singletons. Human reproduction (Oxford, England). 2002;17(4):1081–5.
Muller F, Dreux S, Lemeur A, Sault C, Desgres J, Bernard MA, et al. Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome. Prenat Diagn. 2003;23(13):1073–6.
Mara M, Koryntova D, Rezabek K, Kapral A, Drbohlav P, Jirsova S, et al. Thromboembolic complications in patients undergoing in vitro fertilization: retrospective clinical study. Ceska gynekologie. 2004;69(4):312–6.
Simcox LE, Ormesher L, Tower C, Greer IA. Pulmonary thrombo-embolism in pregnancy: diagnosis and management. Breathe (Sheffield, England). 2015;11(4):282–9.
Aurousseau MH, Samama MM, Belhassen A, Herve F, Hugues JN. Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports. Human reproduction (Oxford, England). 1995;10(1):94–7.
Siering U, Eikermann M, Hausner E, Hoffmann-Esser W, Neugebauer EA. Appraisal tools for clinical practice guidelines: a systematic review. PLoS One. 2013;8(12):e82915.
Bonduelle M, Van Assche E, Joris H, Keymolen K, Devroey P, Van Steirteghem A, et al. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Human reproduction (Oxford, England). 2002;17(10):2600–14.
Janvier A, Spelke B, Barrington KJ. The epidemic of multiple gestations and neonatal intensive care unit use: the cost of irresponsibility. J Pediatr. 2011;159(3):409–13.
Elster N. Less is more: the risks of multiple births. The Institute for Science, law, and technology working group on reproductive technology. Fertil Steril. 2000;74(4):617–23.
Evans MI, Berkowitz RL, Wapner RJ, Carpenter RJ, Goldberg JD, Ayoub MA, et al. Improvement in outcomes of multifetal pregnancy reduction with increased experience. Am J Obstet Gynecol. 2001;184(2):97–103.
Calhoun KC, Barnhart KT, Elovitz MA, Srinivas SK. Evaluating the association between assisted conception and the severity of preeclampsia. ISRN obstetrics and gynecology. 2011;2011:928592.
Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, et al. Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia. Human reproduction (Oxford, England). 2010;25(1):265–74.
Welmerink DB, Voigt LF, Daling JR, Mueller BA. Infertility treatment use in relation to selected adverse birth outcomes. Fertil Steril. 2010;94(7):2580–6.
Smith GN, Walker M, Tessier JL, Millar KG. Increased incidence of preeclampsia in women conceiving by intrauterine insemination with donor versus partner sperm for treatment of primary infertility. Am J Obstet Gynecol. 1997;177(2):455–8.
Wiggins DA, Main E. Outcomes of pregnancies achieved by donor egg in vitro fertilization--a comparison with standard in vitro fertilization pregnancies. Am J Obstet Gynecol. 2005;192(6):2002–6 discussion 6-8.
Klatsky PC, Delaney SS, Caughey AB, Tran ND, Schattman GL, Rosenwaks Z. The role of embryonic origin in preeclampsia: a comparison of autologous in vitro fertilization and ovum donor pregnancies. Obstet Gynecol. 2010;116(6):1387–92.
Wilson RD, Genetics C, Wilson RD, Audibert F, Brock JA, Carroll J, et al. Pre-conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic acid-sensitive congenital anomalies. J Obstet Gynaecol Can. 2015;37(6):534–52.
LeFevre ML. Force USPST. Low-dose aspirin use for the prevention of morbidity and mortality from preeclampsia: U.S. preventive services task force recommendation statement. Ann Intern Med. 2014;161(11):819–26.
The authors would like to acknowledge the support of the Society of Obstetricians and Gynaecologists of Canada (SOGC).
This study was supported by the Canadian Institutes of Health Research (CIHR) Institute of Human Development, child and Youth Health (IHDCYH), Clinician-Investigators Program, Grant number MFM – 146444. CIHR was not involved in the design of the study, data collection, analysis, or interpretation.
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All data generated or analysed during this study are included in this published article and its additional files.
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The present study was approved by the Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board.
Consent to participate: Not applicable.
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