Prenatale controles na IVF of ICSI
Uitgangsvraag
Welke extra risico's zijn er verbonden aan prenatale zorg voor zwangere vrouwen die zwanger zijn geworden na IVF/ICSI? Hoe moet de prenatale zorg worden georganiseerd? Zou antenatale zorg voor vrouwen die zwanger zijn geworden na IVF/ICSI aangepast moeten worden? Hebben vrouwen die zwanger zijn geworden na IVF/ICSI een hoger risico op ongunstige maternale en neonatale uitkomsten exclusief aangeboren of genetische afwijkingen dan vrouwen die spontaan zwanger zijn geworden?
Aanbeveling
Er is geen speciale zorg nodig voor zwangerschappen die ontstaan zijn na IVF/ICSI, maar houd rekening met het verhoogde risico op vroeggeboorte, intra-uteriene groeivertraging, hypertensieve ziekte tijdens de zwangerschap en perinatale mortaliteit.
Overwegingen
Considerations – evidence to decision
Pros and cons of the intervention and quality of the evidence
Both clinically and statistically, there are significantly more pregnancy complications and adverse outcomes in pregnancies conceived by IVF/ICSI compared to spontaneously conceived pregnancies: more overall preterm birth, more children with low birth weight, more SGA, more pregnancy-induced hypertension and more perinatal mortality. The grade of evidence however for all outcomes is very low. This is due to the retrospective nature of the primary studies and the high heterogeneity of the studies.
Whether adapted antenatal care for IVF/ICSI pregnancies is superior to care as usual has not yet been explored. What has been explored is the association between IVF/ICSI and adverse pregnancy outcomes. Based on the available evidence, we can conclude that there may be a higher risk of pregnancy-induced hypertension, SGA, LBW, preterm birth and perinatal mortality in pregnancies conceived by IVF/ICSI compared to spontaneously conceived pregnancies, from which it can be concluded that more tailored perinatal care is indicated for this group of women.
In a review article on care plans for pregnancies after IVF/ICSI, only one care plan intended for these women was found (Velez, 2019). Possible benefits of this care plan are not described. A recent review article described that there are no clear extra measures identified to improve maternal and neonatal outcomes in this group of women (Richardson, 2020).
Values and preferences of patients (and their caregivers)
The intervention (adapted or tailor-made antenatal care) has not yet been explored in literature. The goal would be a timely diagnosis of pregnancy complications in pregnant women after IVF/ICSI. It can be expected that women will have a positive attitude towards a more intensified antenatal care.
The tailoring of antenatal care of women after IVF/ICSI should preferably be in consultation with, and after informing of, the women taking the above-mentioned risks into consideration.
It is well-known that pregnant women after IVF/ICSI have more pregnancy-specific anxiety, poorer quality of life but the same level of self-esteem as women who conceived spontaneously (Gourounti, 2016). The individual pregnant woman’s preference should be incorporated into the plan for antenatal care.
Costs
Cost-benefit studies on adapted antenatal care for IVF/ICSI pregnancies are not available.
Acceptability, feasibility and implementation
Adapted or tailor-made antenatal care is possible and feasible. Women conceiving after IVF/ICSI are probably willing to follow an adapted or tailor-made antenatal care schedule.
For care professionals is it important to have knowledge of and to be alert of the possible complications of pregnancies after IVF/ICSI.
Differences between countries
It appeared that regional differences within and between the countries exist in their antenatal care for women whose pregnancies conceived after IVF/ICSI.
This is a brief overview of education and preferred management according to the knowledge of the guideline authors in order to describe the differences between countries. Irrespective of which country, all interventions should be performed after informed consent has been given by the persons involved.
In the United Kingdom, women who conceive following IVF/ICSI treatment are considered to have a higher chance of complications in pregnancy and their antenatal care tends to be co-ordinated by obstetricians and midwives (rather than midwives alone). Many women who have undergone IVF/ICSI have additional risk factors that necessitate increased antenatal surveillance. Risk assessments are performed early in pregnancy for pre-eclampsia and pregnancy-induced hypertension, venous thromboembolism and fetal growth restriction. Depending on this risk assessment, women may be offered low dose aspirin, thromboprophylaxis and additional ultrasound scans to monitor their babies’ growth.
In the Netherlands, a pregnancy conceived after IVF/ICSI is not considered to be a high risk pregnancy. Therefore, no extra interventions are advised for these pregnancies and a woman is transferred to community midwifery care. For ICSI, but not IVF, invasive prenatal testing is still offered due to the risk of sex chromosomal anomalies.
In Belgium, IVF/ICSI is considered as a risk factor for pregnancy complications. The presence of this risk factor, however, does not alter antenatal care.
In Germany, the classification of high risk pregnancies is recorded in the maternity book. IVF/ICSI procedures are not mentioned as a risk factor per se. Yet, factors associated with IVF/ICSI are mentioned in the medical history. Therefore, most, if not all, pregnancies resulting from IVF/ICSI will be graded as high risk pregnancies, requiring special medical attention and closer follow up.
Recommendations
Rational of the recommendation: weighing arguments in favour and against the intervention
Pregnancies conceived by IVF/ICSI are associated with significantly more pregnancy complications than spontaneously conceived pregnancies (± ovulation induction and intrauterine insemination): more (spontaneous) preterm birth, more low birth weight (birth weight <2500 g), more small for gestational age (birth weight < p10), more hypertensive disorders of pregnancy and more perinatal mortality. The grade of evidence is low, mainly due to the retrospective nature of the primary studies and the heterogeneity in definitions and outcomes. The fact that these pregnancies are associated with more adverse outcomes, warrants different antenatal care compared to spontaneously conceived pregnancies. How antenatal care should be organized, or which preventive measures should be taken, is yet to be explored. In particular, it is important to realise that it is not yet known if adapted antenatal care will result in better perinatal outcomes.
Onderbouwing
Achtergrond
In high resource settings, 1-5% of all children are born after assisted reproductive technology (ART), more specifically IVF/ICSI. Currently, in the planning of antenatal care no distinction is made between women who conceived spontaneously and women who conceived after IVF/ICSI. However, are pregnancies after IVF/ICSI more at risk for pre-eclampsia, intrauterine growth restriction or other pregnancy complications? If this is the case, should the antenatal monitoring plan for women pregnant after IVF/ICSI be adapted accordingly? What are the risks of adverse maternal and neonatal outcomes when women conceived by IVF/ICSI compared to women who conceived spontaneously?
Conclusies
Conclusions
|
Very low GRADE |
ART may increase the risk of overall preterm birth, but the evidence is very uncertain.
Sources: (Qin, 2016.) |
|
Very low GRADE |
ART may increase the risk of low birth weight, but the evidence is very uncertain.
Sources: (Qin, 2016.) |
|
Very low GRADE |
ART may increase the risk of small for gestational age, but the evidence is very uncertain.
Sources: (Qin, 2016.) |
|
Very low GRADE |
ART may increase the risk of pregnancy-induced hypertension, but the evidence is very uncertain.
Sources: (Qin, 2016). |
|
Very low GRADE |
ART may increase the risk of perinatal mortality, but the evidence is very uncertain.
Sources: (Qin, 2016.) |
Samenvatting literatuur
Summary of literature
Description of studies
One systematic review was included (Qin, 2016). In the SR by Qin 50 original cohort studies, published before March 2015 in English or Chinese, were included, comprising 161,370 ART (IVF or ICSI) and 2,280,241 spontaneously conceived singleton pregnancies (women with no history of infertility and no infertility treatment or whose spontaneous pregnancies have arisen after ovulation induction or intrauterine insemination). At least 16 outcomes were reported, including preterm birth, low birth weight, SGA, pregnancy induced hypertension and perinatal mortality. Subgroup and sensitivity analyses that were performed to assess the potential influence of confounding and bias, did not change the overall results (presented below). However, the review authors graded the evidence as very low because of the observational nature of the included studies and heterogeneity.
Results
In the included systematic review, pregnancies after IVF/ICSI were found to be associated with a higher risk of pregnancy complications (hypertensive disorders, preeclampsia) and unfavorable pregnancy outcomes (preterm birth, low birth weight, small for gestational age, perinatal mortality) than spontaneous conceptions. The pooled Risk Ratios or Odds Ratios (all random effects models) as reported in the systematic review are shown below.
1. Overall preterm birth (<37 weeks of gestation). RR (95% CI) 1.71 (1.59 to 1.83) favoring spontaneous conception; heterogeneity (I2): 80% (Qin, 2016).
2. Low Birth Weight (birth weight <2,500 g). RR (95% CI) 1.61 (1.49 to 1.75) favoring spontaneous conception; heterogeneity (I2): 80% (Qin, 2016).
3. Small for Gestational Age (birth weight below the 10th percentile of the national reference curve). RR (95% CI) 1.35 (1.20 to 1.52) favoring spontaneous conception; heterogeneity (I2): 82% (Qin, 2016).
4. Pregnancy-induced hypertension. RR (95% CI) 1.30 (1.04 to 1.62) favoring spontaneous conception; heterogeneity (I2): 79% (Qin, 2016).
5. Perinatal mortality. RR (95% CI) 1.64 (1.41 to 1.90) favoring spontaneous conception; heterogeneity (I2): 45% (Qin, 2016).
Level of evidence of the literature
1. The level of evidence regarding the outcome measure overall preterm birth started low and was downgraded by one level because of conflicting results (inconsistency) to very low.
2. The level of evidence regarding the outcome measure low birth weight started low and was downgraded by one level because of conflicting results (inconsistency) to very low.
3. The level of evidence regarding the outcome measure small for gestational age started low and was downgraded by one level because of conflicting results (inconsistency) to very low.
4. The level of evidence regarding the outcome measure pregnancy-induced hypertension started low and was downgraded by one level because of conflicting results (inconsistency) to very low.
5. The level of evidence regarding the outcome measure perinatal mortality started low and was downgraded by one level because of conflicting results (inconsistency) to very low.
Zoeken en selecteren
Search and select
A systematic review of the literature was performed to answer the following question:
P: pregnant women with a singleton pregnancy;
I: who conceived after IVF/ICSI;
C: who conceived spontaneously;
O: pregnancy complications (spontaneous and medical preterm birth (PTB), low birth weight (LBW), SGA (small for gestational age), hypertensive disorders of pregnancy, perinatal mortality, neonatal morbidity and mortality).
Relevant outcome measures
The guideline development group considered (spontaneous) PTB, SGA and pre-eclampsia as crucial outcome measures for decision making; and LBW, perinatal mortality, neonatal morbidity and mortality, other hypertensive disorders of pregnancy as important outcome measures for decision making.
A priori, the guideline development group did not define the outcome measures listed above but used the definitions used in the studies.
The working group defined RR > 1.10 or RR < 0.91 as a minimal clinically (patient) important difference for all outcome measures.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched using relevant search terms until 5th November 2019. The detailed search strategy is depicted under the tab Methods (attached documents). The systematic literature search resulted in 835 hits. Studies were selected based on the following criteria: systematic reviews comparing pre- and perinatal outcomes in pregnant women with singleton pregnancies who conceived after IVF or ICSI with women who conceived spontaneously; the outcomes of interest were perinatal mortality and outcomes that can be detected early and can possibly be influenced by more frequent antenatal monitoring. Therefore, studies reporting only on congenital malformations or outcomes that become apparent after birth were not considered eligible. Thirty studies were initially selected based on title and abstract screening. After reading the full text, 29 studies were excluded (see the table with reasons for exclusion under the tab Methods (attached documents)), and one study was included.
Pregnancies of women that conceived after IVF/ICSI using donor oocytes were excluded. Placenta previa was not considered as a pregnancy complication but as a birth complication. Placenta previa is at least threefold more frequent in pregnancies after IVF/ICSI.
Results
One study was included in the analysis of the literature. Important study characteristics and results are summarized in the evidence table (attached documents). The assessment of the risk of bias is summarized in the risk of bias table (attached documents).
Referenties
- Gourounti, K. (2016). Psychological stress and adjustment in pregnancy following assisted reproductive technology and spontaneous conception: A systematic review. Women & health, 56(1), 98-118.
- Qin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertility and sterility. 2016 Jan 1;105(1):73-85.
- Richardson, A., Taylor, M., Teoh, J. P., & Karasu, T. (2020). Antenatal management of singleton pregnancies conceived using assisted reproductive technology. The Obstetrician & Gynaecologist, 22(1), 34-44.
- Velez, M. P., Hamel, C., Hutton, B., Gaudet, L., Walker, M., Thuku, M., ... & Smith, G. N. (2019). Care plans for women pregnant using assisted reproductive technologies: a systematic review. Reproductive health, 16(1), 1-19.
Evidence tabellen
Evidence tables
|
Study reference |
Study characteristics |
Patient characteristics |
Intervention (I) |
Comparison / control (C)
|
Follow-up |
Outcome measures and effect size |
Comments |
|
Qin, 2016
Study characteristics and results are extracted from the SR (unless stated otherwise) |
SR and meta-analysis of cohort and case-control studies
Literature search up to March 2015
A: Olivennes 1993 B: Verlaenen 1995 C: Wennerholm 1996 D: Wennerholm 1997 E: Reubinoff 1997 F: Dhont 1997 G: Westergaard 1999 H: Dhont 1999 I: Koudstaal 2000 J: Perri 2001 K: Isaksson 2002 L: Koivurova 2002 M: Wang 2002 N: Hansen 2002 O: Place 2003 P: Ochsenkuhn 2003 Q: Katalinic 2004 R: Li 2005 S: Klemetti 2005 T: Olson 2005 U: Bonduelle 2005 V: Agarwal 2005 W: Ombelet 2005 X: Kapiteijn 2006 Y: Romundstad 2006 Z: Buckett 2007 AB: Schieve 2007 AC: Palermo 2008 AD: Apantaku 2008 AE: Fujii 2010 AF: Halliday 2010 AG: Pinborg 2010 AH: Wisborg 2010 AI: Wen 2010 AJ: Healy 2010 AK: Pelkonen 2010 AL: Henningsen 2011 AM: Zeng 2011 AN: Hayashi 2012 AO: Hansen 2012 AP: Sagot 2012 AQ: Kuivasaari-Pirinen 2012 AR: Davies 2012 AS: Farhi 2013 AT: Fedder 2013 AU: Malchau 2013 AV: Wennerholm 2013 AW: Poon 2013 AX: Marino 2014
Study design: 21 prospective and 29 retrospective cohort studies
Setting and Country: A: clinic, France B: clinic, Belgium C: clinic, Sweden D: clinic, Sweden E: clinic, Israel F: population, Belgium G: population, Denmark H: population, Belgium I: clinic, Netherlands J: clinic, Israel K: clinic, Finland L: population, Finland M: clinic, Australia N: clinic, Australia O: clinic, Belgium P: clinic, Germany Q: population, Germany R: clinic, China S: population, Finland T: clinic, USA U: population, UK, Belgium, Sweden, Denmark and Greece V: clinic, Singapore W: population, Belgium X: population, Netherlands Y: population, Norway Z: clinic, Canada AB: population, USA AC: clinic, USA AD: clinic, UK AE: population, Japan AF: population, Australia AG: population, Denmark AH: population, Denmark AI: clinic, Canada AJ: population, Australia AK: population, Finland AL: population, Denmark AM: clinic, China AN: population, Japan AO: population, Australia AP: population, France AQ: population, Finland AR: population, Australia AS: population, Israel AT: population, Denmark AU: clinic, Denmark AV: population, Denmark, Norway and Sweden AW: clinic, Singapore AX: population, Australia
Source of funding: SR Project Funded by China Postdoctoral Science Foundation (2015M572248) and Hunan Provincial Science and Technology Plan Project (2015RS4055); individual studies: unknown Conflicts of interest: SR authors: none; individual studies: not reported by Qin et al.
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Inclusion criteria SR: published in Chinese or English; prospective or retrospective cohort design; ART (IVF and/or ICSI) singleton pregnancies; pregnancy-related complications and adverse pregnancy outcomes; reporting of RR or OR with 95% CI or data to calculate them
Exclusion criteria SR: review articles, non– peer-reviewed local and/or federal government reports, and conference abstracts and presentations
50 studies included
N; Crude (C), Adjusted (A) or Matched (M)(‘for a wide range of potential confounders for poor outcomes, such as maternal age, education, parity, race, occupation, smoking during pregnancy, socioeconomic status, date of delivery, area of residence, and obstetric and medical history, as well as fetal sex, year of birth, and number at birth’): A: I 162, C 5,096; C B: I 140, C 140; M C: I 140, C 9,753; M D: I 320, C 160; M E: I 260, C 260; M F: I 311, C 622; M G: I 1,298, C 1,298; M H: I 3,048, C 3,048; M I: I 307, C 307; M J: I 95, C 190; M K: I 69, C 345; M L: I 153, C 287; M M: I 1,019, C 1,019; M N: I 713, C 3,906; C O: I 118, C 59; M P: I 163, C 322; M Q: I 2,055, C 7,861; C R: I 115, C 1,095; M S: I 2,930, C 26,489; A T: I 645, C 4,590; M U: I 977, C 538; M V: I 41, C 147; M W: I 1,655, C 3,278; M X: I 2,239, C 6,343; A Y: I 5,581, C 826,909; A Z: I 237, C 338; M AB: I 1,400, C 1,400; M AC: I 229, C 194; M AD: I 88, C 88; M AE: I 1,408, C 53,939; A AF: I 6,946, C 20,838; M, A AG: I 11,286, C 4,800; C AH: I 742, C 16,525; A AI: I 568, C 1,100; M, A AJ: I 6,730, C 24,619; M, A AK: I 4,772, C 31,243; C AL: I 3,881, C 3,880; A AM: I 52, C 52; C AN: I 4,570, C 4,264; M AO: I 1,972, C 205,641; C AP: I 903, C 4,044; M, A AQ: I 255, C 26,870; C AR: I 4,333, C 295,220; C AS: I 509, C 587; A AT: I 17,216, C 33,852; C AU: I 16,732, C 33,437; C AV: I 48,889, C 288,542; C AW: I 261, C 15,985; C AX: I 2,338, C 293,684; A
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A: IVF B: IVF C: ICSI D: IVF E: IVF F: IVF/ICSI (not separately) G: IVF/ICSI (not separately) H: IVF/ICSI (not separately) I: IVF J: IVF/ICSI (not separately) K: IVF/ICSI (not separately) L: IVF M: IVF/ICSI (not separately) N: IVF; ICSI O: IVF; ICSI P: IVF Q: ICSI R: IVF S: IVF T: IVF U: IVF; ICSI V: ICSI W: ICSI X: IVF Y: IVF/ICSI (not separately) Z: IVF; ICSI AB: IVF/ICSI (not separately) AC: ICSI AD: IVF/ICSI (not separately) AE: IVF AF: IVF; ICSI AG: IVF; ICSI AH: IVF/ICSI (not separately) AI: IVF/ICSI (not separately) AJ: IVF/ICSI (not separately) AK: IVF/ICSI (not separately) AL: IVF/ICSI (not separately) AM: IVF/ICSI (not separately) AN: IVF AO: IVF/ICSI (not separately) AP: IVF AQ: IVF/ICSI (not separately) AR: IVF; ICSI AS: IVF; ICSI AT: IVF; ICSI AU: IVF; ICSI AV: IVF/ICSI (not separately) AW: IVF/ICSI (not separately) AX: IVF; ICSI
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A: SC, excluding OI and IUI B: SC, excluding OI and IUI C: SC (not reported whether OI and IUI were included or not) D: SC E: SC F: SC G: SC H: SC, excluding OI and IUI I: SC, excluding OI and IUI J: SC K: SC L: SC M: SC, excluding OI and IUI N: SC, including OI and IUI O: SC, excluding OI and IUI P: SC Q: SC R: SC S: SC, excluding OI and IUI T: SC, excluding OI and IUI U: SC V: SC W: SC X: SC, excluding OI and IUI Y: SC Z: SC AB: SC, excluding OI and IUI AC: SC AD: SC, excluding OI and IUI AE: SC, excluding OI and IUI AF: SC, including OI and IUI AG: SC, including OI and IUI AH: SC, excluding OI and IUI AI: SC AJ: SC, excluding OI and IUI AK: SC AL: SC AM: SC AN: SC, excluding OI and IUI AO: SC, including OI and IUI AP: SC, excluding OI and IUI AQ: SC AR: SC, excluding OI and IUI AS: SC AT: SC, including OI and IUI AU: SC AV: SC AW: SC, excluding OI and IUI AX: SC, excluding OI and IUI
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End-point of follow-up:
end of pregnancy
For how many participants were no complete outcome data available? (intervention/control)
not reported
|
Outcome measure-1 Defined as preterm birth (birth at <37 weeks' gestation)
Effect measure: not reported per study; 36 studies, I 133,338, C 1,289,549 A: Olivennes 1993 B: Verlaenen 1995 D: Wennerholm 1997 E: Reubinoff 1997 F: Dhont 1997 G: Westergaard 1999 H: Dhont 1999 I: Koudstaal 2000 J: Perri 2001 K: Isaksson 2002 L: Koivurova 2002 M: Wang 2002 N: Hansen 2002 P: Ochsenkuhn 2003 Q: Katalinic 2004 V: Agarwal 2005 W: Ombelet 2005 X: Kapiteijn 2006 Z: Buckett 2007 AB: Schieve 2007 AD: Apantaku 2008 AG: Pinborg 2010 AK: Pelkonen 2010 AL: Henningsen 2011 AM: Zeng 2011 AN: Hayashi 2012 AO: Hansen 2012 AQ: Kuivasaari-Pirinen 2012 AR: Davies 2012 AS: Farhi 2013 AT: Fedder 2013 AU: Malchau 2013 AV: Wennerholm 2013 AW: Poon 2013 AX: Marino 2014 Pooled effect (random effects model): RR [95% CI] 1.71 [1.59–1.83] favoring SC Heterogeneity (I2): 80%
Outcome measure-2 Defined as Low Birth Weight (birth weight <2,500 g)
Effect measure: not reported per study; 36 studies, I 130,147, C 1,062,445 A: Olivennes 1993 B: Verlaenen 1995 C: Wennerholm 1996 D: Wennerholm 1997 E: Reubinoff 1997 F: Dhont 1997 G: Westergaard 1999 H: Dhont 1999 I: Koudstaal 2000 K: Isaksson 2002 L: Koivurova 2002 N: Hansen 2002 P: Ochsenkuhn 2003 Q: Katalinic 2004 R: Li 2005 T: Olson 2005 V: Agarwal 2005 W: Ombelet 2005 X: Kapiteijn 2006 Z: Buckett 2007 AA: Poikkeus 2007 AB: Schieve 2007 AD: Apantaku 2008 AE: Fujii 2010 AG: Pinborg 2010 AK: Pelkonen 2010 AL: Henningsen 2011 AN: Hayashi 2012 AO: Hansen 2012 AQ: Kuivasaari-Pirinen 2012 AS: Farhi 2013 AT: Fedder 2013 AU: Malchau 2013 AV: Wennerholm 2013 AW: Poon 2013 AX: Marino 2014 Pooled effect (random effects model): RR [95% CI] 1.61 [1.49 to 1.75] favoring SC Heterogeneity (I2): 80%
Outcome measure-3 Defined as Small for Gestational Age (birth weight below the 10th percentile of the national reference curve)
Effect measure: not reported per study; 14 studies, I 81,090, C 753,771 A: Olivennes 1993 D: Wennerholm 1997 E: Reubinoff 1997 I: Koudstaal 2000 K: Isaksson 2002 AA: Poikkeus 2007 AE: Fujii 2010 AK: Pelkonen 2010 AN: Hayashi 2012 AQ: Kuivasaari-Pirinen 2012 AS: Farhi 2013 AU: Malchau 2013 AV: Wennerholm 2013 AX: Marino 2014 Pooled effect (random effects model): RR [95% CI] 1.35 [1.20–1.52] favoring SC Heterogeneity (I2): 82%
Outcome measure 4 Defined as pregnancy-induced hypertension Effect measure: not reported per study, 13 studies, I 26,652, C 68,948 A: Olivennes 1993 B: Verlaenen 1995 E: Reubinoff 1997 K: Isaksson 2002 P: Ochsenkuhn 2003 Q: Katalinic 2004 V: Agarwal 2005 AA: Poikkeus 2007 AB: Schieve 2007 AM: Zeng 2011 AN: Hayashi 2012 AS: Farhi 2013 AU: Malchau 2013 Pooled effect (random effects model): RR [95% CI] 1.30 [1.04 – 1.62] favoring SC Heterogeneity (I2): 79%
Outcome measure 5 Defined as perinatal mortality (stillbirth, fetal death, or neonatal death)
Effect measure: not reported per study; 22 studies, I 106,267, C 1,262,997 A: Olivennes 1993 B: Verlaenen 1995 F: Dhont 1997 G: Westergaard 1999 H: Dhont 1999 K: Isaksson 2002 N: Hansen 2002 P: Ochsenkuhn 2003 R: Li 2005 W: Ombelet 2005 AA: Poikkeus 2007 AE: Fujii 2010 AG: Pinborg 2010 AH: Wisborg 2010 AI: Wen 2010 AK: Pelkonen 2010 AN: Hayashi 2012 AO: Hansen 2012 AR: Davies 2012 AT: Fedder 2013 AV: Wennerholm 2013 AX: Marino 2014
Pooled effect (random effects model): RR [95% CI] 1.64 [1.41 – 1.90] favoring SC Heterogeneity (I2): 45%
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Authors’ conclusions: “Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, our study indicated that ART singleton pregnancies are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes when compared with those conceived naturally. Obstetricians should manage these pregnancies as high risk.” “Although restricting analysis to studies that have matched or adjusted confounding factors did not materially alter the combined risk estimate, we still cannot rule out the possibility that residual confounding, including vanishing twins, obesity, allogenic nature of the fetus, and pregnancy intention, could affect the results, because these factors do not explain all of the obstetric risk.”
Level of evidence started low (observational studies) and was downgraded with one level because of inconsistency to a very low GRADE
|
Quality assessment
|
Study
First author, year |
Appropriate and clearly focused question?
Yes/no/unclear |
Comprehensive and systematic literature search?
Yes/no/unclear |
Description of included and excluded studies?
Yes/no/unclear |
Description of relevant characteristics of included studies?
Yes/no/unclear |
Appropriate adjustment for potential confounders in observational studies?
Yes/no/unclear/notapplicable |
Assessment of scientific quality of included studies?
Yes/no/unclear |
Enough similarities between studies to make combining them reasonable?
Yes/no/unclear |
Potential risk of publication bias taken into account?
Yes/no/unclear |
Potential conflicts of interest reported?
Yes/no/unclear |
|
Qin 2016 |
yes |
yes |
unclear |
no |
unclear |
yes |
unclear |
yes |
no |
Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 30-12-2022
Laatst geautoriseerd : 30-12-2022
Geplande herbeoordeling : 01-01-2027
Algemene gegevens
Er is meegelezen vanuit de Nederlandse Vereniging voor Kindergeneeskunde (NVK). De NVK heeft de richtlijn niet geautoriseerd, maar heeft geen bezwaar tegen publicatie.
De Koninklijke Nederlandse Organisatie van Verloskundigen (KNOV) is betrokken geweest bij de ontwikkeling van de richtlijn.
De Patiëntenfederatie Nederland heeft de richtlijn goedgekeurd.
De Vlaamse Vereniging voor Obstetrie en Gynaecologie (VVOG), Royal College of Obstetrics and Gynaecology (RCOG) en Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) zijn betrokken geweest bij de ontwikkeling van de richtlijn.
Regiehouder: NVOG
Validity period
The Board of the Dutch Society of Obstetrics and Gynaecology (NVOG) will assess whether these guidelines are still up-to-date in 2027 at the latest. If necessary, a new working group will be appointed to revise the guideline. The guideline’s validity may lapse earlier if new developments demand revision at an earlier date.
As the holder of this guideline, the NVOG is chiefly responsible for keeping the guideline up to date. Other scientific organizations participating in the guideline or users of the guideline share the responsibility to inform the chiefly responsible party about relevant developments within their fields.
Composition guideline development panel
An international panel for the development of the guidelines was formed in 2019. The panel consisted of representatives from all relevant medical disciplines that are involved in medical care for pregnant women.
All panel members have been officially delegated for participation in the guideline development panel by their (scientific) societies. The panel developed the guidelines in the period from May 2019 until March 2021.
The guideline development panel is responsible for the entire text of this guideline.
Declarations of interests
The Code for the prevention of improper influence due to conflicts of interest was followed (https://storage.knaw.nl/2022-08/Code-for-the-prevention-of-improper-influence-due-to-conflicts-of-interest.pdf).
The working group members have provided written statements about (financially supported) relations with commercial companies, organisations or institutions related to the subject matter of the guideline during the past three years. Furthermore, inquiries have been made regarding personal financial interests, interests due to personal relationships, interests related to reputation management, interest related to externally financed research and interests related to knowledge valorisation. The chair of the guideline development panel is informed about changes in interests during the development process. The declarations of interests are reconfirmed during the commentary phase. The declarations of interests can be requested at the administrative office of the Knowledge Institute of the Dutch Association of Medical Specialists and are summarised below.
Samenstelling werkgroep
Composition guideline development panel
All panel members have been officially delegated for participation in the guideline development panel by their scientific societies. The guideline development panel is responsible for the entire text of this guideline.
Guideline development panel
- J.J. Duvekot, obstetrician, Consultant Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands (chair)
- I. Dehaene, obstetrician, Consultant Obstetrics and Gynaecology, Ghent University Hospital Belgium
- S. Galjaard, obstetrician, Consultant Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands
- A. Hamza, obstetrician, Consultant Obstetrics and Gynaecology, University Medical Center of Saarland, Homburg an der Saar, Germany
- S.V. Koenen, obstetrician, Consultant Obstetrics and Gynaecology, ETZ, locatie Elisabeth Ziekenhuis Tilburg, the Netherlands
- M. Kunze, obstetrician, Consultant Obstetrics and Gynaecology, Department of Gynecology& Obstetrics University of Freiburg, Germany
- M.A. Ledingham, obstetrician, Consultant Obstetrics and Gynaecology, the Queen Elizabeth Hospital Glasgow, UK
- B. Magowan, obstetrician, Consultant Obstetrics and Gynaecology, and Co-Chair UK RCOG Guidelines Committee, NHS Borders, Scotland, UK
- G. Page, obstetrician, Consultant Obstetrics and Gynaecology, Jan Yperman Hospital, Ypres, Belgium
- S.J. Stock, Reader and Consultant in Maternal and Fetal Medicine, University of Edinburgh Usher Institute and NHS Lothian, Edinburgh, Scotland, UK
- A.J. Thomson, obstetrician, Consultant Obstetrics and Gynaecology, Royal Alexandra Hospital (NHS Greater Glasgow and Clyde), UK
- G. Verhulst, obstetrician, Consultant Obstetrics and Gynaecology, ASZ Aalst/Geraardsbergen/Wetteren, Belgium
- D.C. Zondag, midwife/practice owner verloskundige praktijk De Toekomst-Geldermalsen, the Netherlands
Methodological support
- E. den Breejen, senior advisor, Knowledge Institute of the Dutch Association of Medical Specialists (until June 2019)
- J.H. van der Lee, senior advisor, Knowledge Institute of the Dutch Association of Medical Specialists (since May 2019)
- Y. Labeur, junior advisor, Knowledge Institute of the Dutch Association of Medical Specialists
Belangenverklaringen
|
Last name |
Principal position |
Ancillary position(s) |
Declared interests |
Action |
|
Duvekot (chair) |
Consultant Obstetrics and Gynaecology, Erasmus MC, Rotterdam |
Director Medisch Advies en Expertise Bureau Duvekot, Ridderkerk |
none |
none |
|
Dehaene |
Consultant Obstetrics and Gynaecology, Ghent University Hospital |
none |
none |
none |
|
Galjaard |
Consultant Obstetrics and Gynaecology, Erasmus MC, Rotterdam |
Associated member of Diabetes in Pregnancy Group (DPSG) |
none |
none |
|
Hamza |
Consultant Obstetrics and Gynaecology, University Medical Center of Saarland, Homburg |
part of the advisory board of clinical innovations, which produces Kiwi-Vacuum Extractors® and Ebb Balloon Catheter®;
|
gave ultrasound courses sponsored by ultrasound producing companies: Samsung Germany and Matramed |
Recommendations do not involve either vacuum extractor or Ebb catheter (which is used for postpartum hemorrhage); therefore no actions |
|
Koenen |
Consultant Obstetrics and Gynaecology, ETZ, locatie Elisabeth Ziekenhuis Tilburg |
Chairman 'Koepel Kwaliteit' NVOG |
none |
none |
|
Kunze |
Divison Chief, Maternal-Fetal Medicine and Obstetrics, Departement of Gynecology & Obstetrics, University of Freiburg |
none |
none |
none |
|
Ledingham |
Consultant in Maternal and Fetal Medicine, Queen Elizabeth Hospital, Glasgow |
Co-chair RCOG Guidelines committee, Guideline developer for sign (scottisch intercollegiate guidelines group) |
none |
none |
|
Magowan |
Consultant Obstetrics and Gynaecology, and Co-Chair UK RCOG Guidelines Committee, NHS Borders, Scotland |
Co-chair RCOG Guidelines committee |
none |
none |
|
Page |
Consultant Obstetrics and Gynaecology, Jan Yperman Hospital, Ypres |
none |
none |
none |
|
Stock |
Reader and Consultant in Maternal and Fetal Medicine, University of Edinburgh and NHS Lothian, Edinburgh, Scotland, UK |
Consultant Obstetrician and Subspecialist Maternal and Fetal Medicine, member of the NIHR HTA General committee (grant funding board) and Chair of the RCOG Stillbirth Clinical Studies Group |
Research grants paid to the institution for research into pregnancy problems from National Institute of Healthcare Research (NIHR) Health Technology Assessment (HTA), NIHR Global Research Fund, Wellcome Trust, Medical Research Council, Tommy's Baby Charity, Cheif Scientist Office Scotland. Some of this work focuses on improving risk prediction of preterm labour and researching the benefits and harms of antenatal corticosteroids. Non-financial support from HOLOGIC, non-financial support from PARSAGEN, non-financial support from MEDIX BIOCHEMICA during the conduct of an NIHR HTA study in the form of provision of reduced cost assay kits to participating sites and blinded test assay analysers |
none |
|
Thomson |
Consultant Obstetrics and Gynaecology, Royal Alexandra Hospital (NHS Greater Glasgow and Clyde) |
Guideline developer for the RCOG |
none |
none |
|
Verhulst |
Head of Department of Gynaecology and Obstetrics, ASZ Aalst/Geraardsbergen/Wetteren |
none |
none |
none |
|
Zondag |
Midwife/practice owner verloskundige praktijk De Toekomst-Geldermalsen |
Policy adviser at the Dutch association of midwives (KNOV). Teacher at PA clinical midwives - Hogeschool Rotterdam |
none |
none |
Inbreng patiëntenperspectief
Representation of the patient perspective
Involvement of patient representatives from all four participating countries was challenging. Representatives of patient organisations from three countries (UK, Belgium, the Netherlands) commented on the draft guideline texts and discussed these during an online meeting. They represented the RCOG Women’s Network, the Flemish organisation for people with fertility problems ‘De verdwaalde ooievaar’, the Netherlands Patient Federation, and the Dutch association for people with fertility problems ‘Freya’. The comments were discussed and where relevant incorporated by the guideline development panel.
Methode ontwikkeling
Evidence based
Implementatie
Implementation
Guideline implementation and practical applicability of the recommendations was taken into consideration during various stages of guideline development. Factors that may promote or hinder implementation of the guideline in daily practice were given specific attention.
The guideline is distributed digitally among all relevant professional groups. The guideline can also be downloaded from the following websites: www.nvog.nl, www.vvog.be, www.rcog.org.uk, www.dggg.de, and the Dutch guideline website: www.richtlijnendatabase.nl.
Implementation plan
|
Recommendation |
Time needed for implementation: < 1 year, 1 tot 3 years or > 3 years |
Anticipated effect on costs |
Conditions for implementation within designated time frame) |
Possible barriers for implementation1 |
Actions needed for implementation2 |
Who is responsible for actions3 |
Other comments |
|
Consider pregnancies conceived by IVF/ICSI as high risk pregnancies given the increased risks for preterm delivery, fetal growth restriction, hypertensive disorders of pregnancy and perinatal mortality |
< 1 year |
none |
|
|
|
|
|
Werkwijze
Method
AGREE
This guideline has been developed conforming to the requirements of the report of Guidelines for Medical Specialists 2.0 by the advisory committee of the Quality Counsel. This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (www.agreetrust.org)(Brouwers, 2010), a broadly accepted instrument in the international community and on the national quality standards for guidelines: “Guidelines for guidelines” (www.zorginstituutnederland.nl).
Identification of subject matter
During the initial phase of the guideline development the chairman, guideline development panel and the advisor inventoried the relevant subject matter for the guideline. Since this was a pilot project, the content of the questions and the support base in clinical practice was considered of less importance than the process of international collaboration and learning from each other. Key questions were selected in such a way that:
-
- they were relevant for obstetric practice in all collaborating countries;
- it was expected that the amount of literature identified for each question would be reasonable, i.e. some literature was expected, but not much;
- the recommendations were expected not to lead to extensive discussion among working group members because no major controversy was expected;
- there were no recent guidelines available for these particular topics in any of the four countries.
Clinical questions and outcomes
The guideline development panel then formulated definitive clinical questions and defined relevant outcome measures (both beneficial and harmful effects). The working group rated the outcome measures as critical, important and not important. Furthermore, where applicable, the working group defined relevant clinical differences.
Strategy for search and selection of literature
For the separate clinical questions, specific search terms were formulated and published scientific articles were searched for in (several) electronic databases. Furthermore, studies were scrutinized by cross-referencing for other included studies. The studies with potentially the highest quality of research were searched for first. The panel members selected literature in pairs (independently of each other) based on title and abstract. A second selection was performed based on full text. The databases, search terms and selection criteria are described in the modules containing the clinical questions.
Quality assessment of individual studies
Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search, so that risk of bias could be estimated. This is described in the “risk of bias” tables.
Summary of literature
The relevant research findings of all selected articles are shown in evidence tables. The most important findings in literature are described in literature summaries. In case there were enough similarities between studies, the study data were pooled.
Grading quality of evidence and strength of recommendations
The strength of the conclusions of the scientific publications was determined using the GRADE-method. GRADE stands for Grading Recommendations Assessment, Development and Evaluation (see http://www.gradeworkinggroup.org/).
GRADE defines four gradations for the quality of scientific evidence: high, moderate, low or very low. These gradations provide information about the amount of certainty about the literature conclusions (http://www.guidelinedevelopment.org/handbook/).
The basic principles of the GRADE method are: formulating and prioritising clinical (patient) relevant outcome measures, a systematic review for each outcome measure, and appraisal of the evidence for each outcome measure based on the eight GRADE domains (domains for downgrading: risk of bias, inconsistency, indirectness, imprecision, and publication bias; domains for upgrading: dose-effect association, large effect, and residual plausible confounding).
GRADE distinguishes four levels for the quality of the scientific evidence: high, moderate, low and very low. These levels refer to the amount of certainty about the conclusion based on the literature, in particular the amount of certainty that the conclusion based on the literature adequately supports the recommendation (Schünemann, 2013; Hultcrantz, 2017).
|
GRADE |
Definition |
|
High |
|
|
Moderate |
|
|
Low |
|
|
Very low |
|
For the wording of the conclusions we used the statements suggested by the GRADE working group (Santesso, 2020), as shown below.
Source: Santesso (2020)
The limits of clinical decision making are very important in grading the evidence in guideline development according to the GRADE methodology (Hultcrantz, 2017). Exceedance of these limits would give rise to adaptation of the recommendation. All relevant outcome measures and considerations need to be taken into account to define the limits of clinical decision making. Therefore, the limits of clinical decision making are not one to one comparable to the minimal clinically relevant difference. In particular for interventions of low costs and without important drawbacks the limit of clinical decision making regarding the effectiveness of the intervention may be lower (i.e. closer to no effect) than the Minimal Clinically Important Difference (MCID) (Hultcrantz, 2017).
Considerations (evidence to decision)
Aspects such as expertise of working group members, patient preferences, costs, availability of facilities, and organisation of healthcare aspects are important to consider when formulating a recommendation. For each clinical question, these aspects are discussed in the paragraph Considerations, using a structured format based on the evidence-to-decision framework of the international GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello, 2016b). The evidence-to-decision framework is an integral part of the GRADE methodology.
Formulating recommendations
Recommendations provide an answer to the primary question, and are based on the best scientific evidence available and the most important considerations. The level of scientific evidence and the importance given to considerations by the working group jointly determine the strength of the recommendation. In accordance with the GRADE method, a low level of evidence for conclusions in the systematic literature review does not rule out a strong recommendation, while a high level of evidence may be accompanied by weak recommendations. The strength of the recommendation is always determined by weighing all relevant arguments.
Knowledge gaps
During the development of this guideline, systematic searches were conducted for research contributing to answering the primary questions. For each primary question, the working group determined whether (additional) scientific research is desirable.
Commentary and authorisation phase
The concept guideline was subjected to commentaries by the scientific societies and patient organisations involved. The draft guideline was also submitted to the following organisations for comment: RCOG Guideline Committee and RCOG Patient Information Committee, German Neonatology and Peaediatric Intensive Care Association (Gesellschaft für Neonatologie und pädiatrische Intensivmedzin e.V.), German Midwives Society (Deutscher Hebammenverband), Flemish Midwives Society (VBOV), Belgian Federal Knowledge Centre for Health Care (KCE), Flemish College of Maternity and Neonatal Medicine (College Moeder Kind), Flemish patient organization for fertility problems (De Verdwaalde Ooievaar), Dutch Pediatric Society (NVK), Dutch College of General Practitioners (NHG), Healthcare Insurers Netherlands (ZN), The Dutch Healthcare Authority (NZA), the Health Care Inspectorate (IGJ), Netherlands Care Institute (ZIN), Dutch Organisation of Midwives (KNOV), Hospital organization (NVZ), Patient organisations Dutch Patient Federation and Freya. The comments were collected and discussed with the working group. The feedback was used to improve the guideline; afterwards the working group made the guideline definitive. The final version of the guideline was offered for authorization to the involved scientific societies and patient organisations and was authorized or approved, respectively.
Legal standing of guidelines
Guidelines are not legal prescriptions but contain evidence-based insights and recommendations that care providers should meet in order to provide high quality care. As these recommendations are primarily based on ‘general evidence for optimal care for the average patient’, care providers may deviate from the guideline based on their professional autonomy when they deem it necessary for individual cases. Deviating from the guideline may even be necessary in some situations. If care providers choose to deviate from the guideline, this should be done in consultation with the patient, where relevant. Deviation from the guideline should always be justified and documented.
Literature
Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open 2017;7:e018593.
Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ 2016;353:i2016.
Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089.
Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42.
Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13.
Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html
Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.
Santesso, N., Glenton, C., Dahm, P., Garner, P., Akl, E. A., Alper, B., ... & GRADE Working Group. (2020). GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions. Journal of clinical epidemiology, 119, 126-135.
Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.
Schünemann HJ, Oxman AD, Brozek J, Glasziou P, Jaeschke R, Vist GE, Williams JW Jr, Kunz R, Craig J, Montori VM, Bossuyt P, Guyatt GH; GRADE Working Group. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008 May 17;336(7653):1106-10.
Schünemann, A Holger J [corrected to Schünemann, Holger J]. PubMed PMID: 18483053; PubMed Central PMCID: PMC2386626.
Wessels M, Hielkema L, van der Weijden T. How to identify existing literature on patients' knowledge, views, and values: the development of a validated search filter. J Med Libr Assoc. 2016 Oct;104(4):320-324.
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