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Table 4 Detailed recommendations and supporting publications

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

Guideline reference

Population and Recommendations specific to care for women during pregnancy and delivery who became pregnant using ART

Author Year

General ART-pregnancy related recommendations

List of studies cited as informing the recommendationa

Level of evidence (e.g. II-2A)

Alexander 2017 [23]

Recommendation 24: In women who achieve pregnancy following controlled ovarian hyperstimulation, TSH elevations should be treated according to the recommendations for pregnant women in general (Section VII Hypothyroidism and Pregnancy), as outlined below:

Ref 246: Poppe K. Thyroid function after controlled ovarian hyperstimulation in women with and without the hyperstimulation syndrome. Fertil Steril 2011; 96:241–245. Ref 247: Mintziori G. Thyroid function during ovarian stimulation: a systematic review. Fertil Steril 2011; 96:780–785. Ref 248: Muller AF. Decrease of free thyroxine levels after controlled ovarian hyperstimulation. J Clin Endocrinol Metab 2000; 85:545–548. Ref 249: Poppe K. Impact of ovarian hyperstimulation on thyroid function in women with and without thyroid autoimmunity. J Clin Endocrinol Metab 2004; 89:3808–3812. Ref 250: Poppe K. Thyroid function after assisted reproductive technology in women free of thyroid disease. Fertil Steril 2005; 83:1753–1757. Ref 251: Gracia CR. Thyroid function during controlled ovarian hyperstimulation as part of in vitro fertilization. Fertil Steril 2012; 97:585–591. Ref 252: Reinblatt S. Thyroid stimulating hormone levels rise after assisted reproductive technology. J Assist Reprod Genet 2013; 30:1347–1352. Ref 255: Stuckey BG. Thyroxine replacement during super-ovulation for in vitro fertilization: a potential gap in management? Fertil Steril 2010; 93:2414.e1–3. Ref 256: Busnelli A. Thyroid axis dysregulation during in vitro fertilization in hypothyroid-treated patients. Thyroid 2014; 24:1650–1655. Ref 257: Busnelli A. Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF. Eur J Endocrinol 2015; 173:417–424. Ref 258: Davis LB. The effect of infertility medication on thyroid function in hypothyroid women who conceive. Thyroid 2007; 17:773–777.

Weak recommendation, moderate-quality evidence

Recommendation 25: In the setting of pregnancy, maternal hypothyroidism is defined as a TSH concentration elevated beyond the upper limit of the pregnancy-specific reference range.

Ref 17: Li C et al. Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women? J Clin Endocrinol Metab 2014; 99:73–79. Ref 19: Korevaar TI, Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study. J Clin Endocrinol Metab 2013; 98:4382–4390 Ref 24 Bestwick JP et al. Thyroid stimulating hormone and free thyroxine in pregnancy: expressing concentrations as multiples of the median (MoMs). Clin Chim Acta 2014; 430:33–37. Ref 265: La’ulu SL, Roberts WL. Ethnic differences in first trimester thyroid reference intervals. Clin Chem 2011; 57:913–915. Ref 266: Mannisto T et al. Early pregnancy reference intervals of thyroid hormone concentrations in a thyroid antibody-negative pregnant population. Thyroid 2011; 21:291–298. Ref 267: Medici M, et al. Maternal early pregnancy and newborn thyroid hormone parameters: the Generation R study. J Clin Endocrinol Metab 2011; 97:646–652. Ref 268. Springer D et al. Reference intervals in evaluation of maternal thyroid function during the first trimester of pregnancy. Eur J Endocrinol 2009; 160:791–797. Ref 269: Medici M, et al. Thyroid function in pregnancy: what is normal? Clin Chem 2015 61:704–713.

Strong recommendation, high-quality evidence

Recommendation 26: The pregnancy-specific TSH reference range should be defined as follows:

a) When available, population- and trimester-specific reference ranges for serum TSH during pregnancy should be defined by a provider’s institute or laboratory and should represent the typical population for whom care is provided. Reference ranges should be defined in healthy TPOAb-negative pregnant women with optimal iodine intake and without thyroid illness. When this goal is not feasible, pregnancy-specific TSH reference ranges obtained from similar patient populations and performed using similar TSH assays should be substituted. (Strong recommendation, high-quality evidence)

b) If internal or transferable pregnancy-specific TSH reference ranges are not available, an upper reference limit of *4.0 mU/L may be used. For most assays, this limit represents a reduction in the nonpregnant TSH upper reference limit of *0.5 mU/L

a) Strong recommendation, high-quality evidence

b) Strong recommendation, high-quality evidence

c) Strong recommendation, moderate-quality evidence

American College of Obstetricians & Gynecologists 2016 [25]

Recommendation: When a higher-order (triplet or more) multifetal pregnancy is encountered, the option of multifetal reduction should be discussed. In the case of a continuing higher-order multifetal pregnancy, ongoing obstetric care should be with an obstetrician–gynecologist or other obstetric care provider and at a facility capable of managing anticipated risks and outcomes.

Ref 9: American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 553: multifetal pregnancy reduction. Obstet Gynecol. 2013;121(2 Pt 1):405-410.(33) Ref 27: Wimalasundera RC. Selective reduction and termination of multiple pregnancies. Semin Fetal Neonatal Med 2010; 15:327-335. Ref 30: Dodd JM. Reduction of the number of fetuses for women with a multiple pregnancy. Cochrane Database of Systematic Reviews 2015, Issue 11. Art. No.: CD003932. pub3

Not stated

"When a patient request for multifetal pregnancy reduction is discordant with the physician's value system, the patient should be referred to a physician with expertise in performing multifetal pregnancy reductions."

Ref 9: American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 553: multifetal pregnancy reduction. Obstet Gynecol. 2013;121(2 Pt 1):405-410.(33)

Not stated

"…, it seems judicious to make patients aware of the low level risk of birth defects and to offer ultrasonographic surveillance for structural abnormalities in these pregnancies. Some professional organizations recommend fetal echocardiography in all ART pregnancies, but the incremental yield of such studies after a targeted ultrasonography that is reassuring is unclear and needs to be balanced against available resources. Of course, patient-specific risks identified during evaluation of a patient's medical history may indicate need for specific studies or other fetal evaluation during pregnancy."

Ref 56: American Institute of Ultrasound in Medicine, AIUM Practice Parameter for the performance of fetal echocardiography. Laurel (MD): AIUM; 2013. Available at: http://www.aium.org/resources/guidelines/fetalEcho.pdf. Ref 57: Donofrio MT. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. American Heart Association Adults with Congenital Heart Disease Joint Committee of the Council on Cardiovascular Disease in the Young and Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Council on Cardiovascular and Stroke Nursing. Circulation 2014; 129:2183-242.

Not stated

ASRM 2015 [24]

Recommendation: Levothyroxine treatment may improve pregnancy outcomes in women with positive thyroid antibodies, especially if the TSH level is over 2.5 mlU/L.

Ref 48: Kutteh WH Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction. Fertil Steril 1999; 71: 843–8. Ref 49: Poppe K. Assisted reproduction and thyroid autoimmunity: an unfortunate combination? J Clin Endocrinol Metab 2003; 88: 4149–52. Ref 54: Singh A. Presence of thyroid antibodies in early reproductive failure: biochemical versus clinical pregnancies. Fertil Steril 1995; 63: 277–81. Ref 55: Negro R. Euthyroid women with autoimmune disease undergoing assisted reproduction technologies: the role of autoimmunity and thyroid function. J Endocrinol Invest 2007; 30:3–8. Ref 56: Negro R. Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study. Hum Reprod 2005; 20:1529–33

Not clear

Bates 2012 [27]

Recommendation 5.1.1: For women undergoing assisted reproduction, we recommend against the use of routine thrombosis prophylaxis.

Ref 116: Mára M. Thromboembolic complications in patients undergoing in vitro fertilization: retrospective clinical study [in Czech]. Ceska Gynekol 2004; 69 (4): 312 - 316. Ref 117: Aurousseau MH. Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports. Hum Reprod 1995; 10 (1): 94-97. Ref 121: Jacobsen AF. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (6): 905-912. Ref 136: Hull RD. Extended out-of hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001; 135 (10): 858-869.

Grade 1B

Recommendation 5.1.2: For women undergoing assisted reproduction who develop severe ovarian hyperstimulation syndrome, we suggest thrombosis prophylaxis (prophylactic LMWH) for 3 months postresolution of clinical ovarian hyperstimulation syndrome rather than no prophylaxis.

Ref 115: Nelson SM. Prophylaxis of VTE in women-during assisted reproductive techniques. Thromb Res 2009; 123 (suppl 3): S8-S15. Ref 116: Mára M. Thromboembolic complications in patients undergoing in vitro fertilization: retrospective clinical study [in Czech] Ceska Gynekol 2004; 69 (4): 312-316. Ref 122: Chan WS. T he ‘ART’ of thrombosis: a review of arterial and venous thrombosis in assisted reproductive technology. Curr Opin Obstet Gynecol 2009; 21 (3): 207-218.

Grade 2C

Chan 2014 [26]

Recommendation 41: Women who develop a venous thromboembolism in association with the use of assisted reproductive technology and conceive, follow recommendation 12 and 13.

see below

see below

Recommendation 12: For pregnant women with an acute venous thromboembolism we recommend therapeutic anticoagulation for a minimum of 3 months.

" ... evidence confirming or disputing the safety of this option is unavailable" pg 535

I-A

Unsure what they are basing this on

Recommendation 13: Following initial treatment, anticoagulation intensity can be decreased to intermediate or prophylactic dose for the remainder of the pregnancy and for at least 6 weeks postpartum12 and 13 for acute venous thromboembolism in pregnancy.

"….evidence confirming or disputing the safety of this option is unavailable." pg 535

III-C

Unsure what they are basing this on

Recommendation 59 (b): Postpartum thromboprophylaxis should be considered in the presence of multiple clinical or pregnancy-related risk factors when the overall absolute risk is estimated to be greater than 1% : (b) in any 3 or more of the following risk factors (each with an absolute risk of venous thromboembolism < 1% in isolation): (i) age >35 years; (ii); parity ≥2; (iii) any assisted reproductive technology; (iv) multiple pregnancy; (v) placental abruption; (vi) premature rupture of membranes; (vii) elective Caesarean section; (viii) maternal cancer.

Ref 109: Jacobsen AF. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case–control study. J Thromb Haemost 2008; 6:905–12.

II-2B

Chitayat 2011 [19]

Recommendation 4b: Invasive prenatal diagnosis for cytogenetic analysis should not be performed without multiple marker screening results except for women who are at increased risk of fetal aneuploidy because the pregnancy was conceived by in vitro fertilization with intracytoplasmic sperm injection.

Ref 4: Bonduelle M. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod 2002; 17:2600–14.

II-2E

Recommendation 13: Information such as gestational dating, maternal weight, ethnicity, insulin-dependent diabetes mellitus, and use of assisted reproduction technologies should be provided to the laboratory to improve accuracy of testing.

Ref 96: Barkai G. Down’s syndrome screening marker levels following assisted reproduction. Prenat Diagn 1996; 16:1111–4. Ref 97: Wald NJ. Serum markers for Down’s syndrome in women who have had in vitro fertilisation: implications for antenatal screening. Br J Obstet Gynaecol 1999; 106:1304–6. Ref 98: Perheentupa A. Maternal serum beta-HCG and alpha-fetoprotein concentrations in singleton pregnancies following assisted reproduction. Hum Reprod 2002; 17:794–7. Ref 99: Raty R. Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down’s syndrome. Hum Reprod 2002; 17:481–4. Ref 100: Maymon R. Serial first- and second-trimester Down’s syndrome screening tests among IVF-versus naturally-conceived singletons. Hum Reprod 2002; 17:1081–5. Ref 101: Maymon R. Integrated first- and second-trimester Down syndrome screening test among unaffected IVF pregnancies. Prenat Diagn 2004; 24:125–9. Ref 102: Muller F. French Collaborative Group. Medically assisted reproduction and second trimester maternal serum marker screening for Down syndrome. Prenat Diagn 2003; 23:1073–6. Ref 103: Liao AW. First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction. Hum Reprod 2001; 16:1501–4. Ref 104: Orlandi F. First trimester screening with free beta-hCG, PAPP-A and nuchal translucency in pregnancies conceived with assisted reproduction. Prenat Diagn 2002; 22:718–21. Ref 105: Bellver J. First trimester biochemical screening for Down’s syndrome in singleton pregnancies conceived by assisted reproduction. Hum Reprod 2005; 20:2623–7. Ref 106: Hui PW. Nuchal translucency in pregnancies conceived after assisted reproduction technology. Ultrasound Obstet Gynecol 2005; 25:234–8.

II-2A

Gameiro 2015 [21]

Recommendation under section 4.3 (b): The guideline development group recommends that fertility staff refer patients who experience or are at risk of experiencing clinically significant psychosocial problems after successful treatment, to specialized psychosocial care (infertility counselling or psychotherapy).

Glade AC, Bean RA, Vira R. A Prime Time for Marital/Relational Intervention: A Review of the Transition to Parenthood Literature with Treatment Recommendations. Am J Fam Ther 2005;33: 319-336.

Good practice points based on expert opinion

Recommendation under section 4.3 (b): The guideline development group recommends that fertility staff offer additional psychosocial care to patients at risk of increased infertility-specific psychosocial distress after successful treatment.

Hammarberg K, Fisher JR, Wynter KH. Psychological and social aspects of pregnancy, childbirth and early parenting after assisted conception: a systematic review. Hum Reprod Update 2008;14: 395-414

Good practice points based on expert opinion

Recommendation under section 4.3 (b): The guideline development group recommends that fertility staff offer patients the opportunity to discuss their worries about pregnancy achieved with fertility treatment.

Ref 1: Vilska S. Mental health of mothers and fathers of twins conceived via assisted reproduction treatment: a 1-year prospective study. Hum Reprod 2009; 24: 367-377. Ref 2: Baor L. Mothers of IVF and spontaneously conceived twins: a comparison of prenatal maternal expectations, coping resources and maternal stress. Hum Reprod 2010; 25: 1490-1496.

Good practice points based on expert opinion

Okun 2014 [18]

Recommendation 6: There is a role for closer obstetric surveillance of women who conceive with assisted human reproduction

No references cited for this recommendation

III-L

Recommendation 10: In pregnancies achieved by artificial reproductive technology, routine anatomic ultrasound for congenital structural abnormalities is recommended between 18 and 22 weeks.

Ref 28: Zhu JL. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ 2006; 333:679. Ref 38: Davies GA. Obesity in pregnancy. Society of Obstetricians and Gynaecologists of Canada Clinical Practice Guideline, No. 239, February 2010. J Obstet Gynaecol Can 2010; 32:165–73. Ref 149: Wennerholm UB. Incidence of congenital malformations in children born after ICSI. Hum Repro 2000; 15:944-8. Ref 150: Reefhuis J. Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod 2009; 24:360–6. Ref 151: Wen SW. A comprehensive assessment of outcomes in pregnancies conceived by in vitro fertilization/ intracytoplasmic sperm injection. Eur J Obstet Gynecol Reprod Biol 2010; 150:160–5. Ref 152: Hansen M. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002; 346:725-30. Ref 153: Katalinic A. Pregnancy course and outcome after intracytoplasmic sperm injection: a controlled, prospective cohort study. Fertil Steril 2004; 1:1604-16.

II-2A

Some discrepancies between references in text and those in reference list.

Recommendation 11: Pregnancies conceived by intracytoplasmic sperm injection may be at increased risk of chromosomal aberrations, including sex chromosome abnormalities. Diagnostic testing should be offered after appropriate counselling

Ref 149: Wennerholm UB. Incidence of congenital malformations in children born after ICSI. Hum Reprod 2000; 15:944–8. Ref 155: Bonduelle M. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod 2002; 17:2600–14. Ref 156: Feng C. Assisted reproductive technology may increase clinical mutation detection in male offspring. I 2008; 90:92–6. Ref 158: Ranta JK. Increased time-to-pregnancy and first trimester Down's syndrome screening. Hum Reprod 2010: 25:412-7. Ref 159: Amore DJ. Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome. Hum Reprod 2009; 24:1330-8. Ref 160: Shulman LP. Maternal serum analyte levels after first-trimester multifetal pregnancy reduction. Am J Obstet Gynecol 1996; 174:1072-4. Ref 161: Shulman A. Mid-gestation Down syndrome screening test and pregnancy outcome among unstimulated assisted-conception pregnancies. Prenat Diagn 2003; 23:625-8.

II-2A

Some discrepancies between references in text and those in reference list.

RANZCOG [22]

IVF or GIFT pregnancy should be referred to a GP (with a recognised postgraduate qualification in obstetrics) or Specialist Obstetrician where a GP with suitable qualifications is not available, referral should be to a specialist Obstetrician.

There are no references in this publication.

Unknown

Thorne and Wischmann [20]

Recommendation 3.6: During medical treatment and pregnancy, both partners may develop ambivalent feelings towards the fact that the female partner carries the semen of an unknown man or has become pregnant with this semen. Counselling can contribute towards an understanding to such reactions and help in managing them.

References were not linked to recommendations. A list of references are included in this publication, but other than the introduction section, none of contained within the remaining of the document.

None stated

  1. aOnly the first author is listed in the bibliographic reference