Heparin
Low-molecular weight heparin is used for a variety of indications, such
as pulmonary embolus or deep vein thrombosis, and inherited or acquired
thrombophilia (53). There are several papers that examine the use of
heparin in patients who have repeated ART cycle failure to improve
reproductive outcomes, however there were no papers found that examine
the effect of long-term heparin therapy for comorbid medical conditions
on ART outcomes.
Conclusion
Whilst prescription drug use amongst men and women of child-bearing age
is common, use of individual medications is uncommon and given the
ethical issues of performing randomised control trials using medications
of unknown safety in pregnant women and unborn foetuses, evidence is
limited to observational studies and history of previous use.
Furthermore, there are some acute and or chronic medical conditions that
must be treated in pregnancy to ensure overall health of the mother,
father and baby. Adverse outcomes that have been reported are often rare
including congenital malformations and stillbirth and therefore is
difficult to determine any correlation of risk with one specific
medication. As such the impact of medication exposure prior to and
during ART treatments is challenging to determine. However, with more
couples choosing to delay conception and hence often seek fertility
treatment at an older age, couples are more likely to have comorbid
medical conditions and hence be taking prescription drugs. Depression in
particular is common in men and women of child-bearing age, with suicide
rates rising rates amongst young men and is now the leading cause of
late direct maternal death (54, 55). Couples with a history of low mood
can suffer with an exacerbation of symptoms following an unexpected
delay in fertility and subsequent stressful investigations and
treatment. Therefore it is vitally important that we have accurate and
up to date information to facilitate shared decision making in regards
to continuing antidepressant treatment versus alternative
non-pharmacological therapies prior to and during ART.
Health promotion through lifestyle factors including smoking cessation
to target better asthma control and weight loss to reduce the rates of
type II diabetes and gastric-oesophageal reflux disease may also improve
patients overall health, reduce the need for prescription drug use and
improve reproductive outcomes following ART.
Further research is required on prescription drug use amongst men and
women and the impact on reproductive outcomes. Formal clinical
guidelines are encouraged to standardise how couples are counselled and
enable patients to make informed decisions about their own health and
medication use during ART and throughout the pregnancy.
Disclosure of Interests
The authors declare that they have no relevant conflicts of interest,
nor any interests to disclose.
Contribution to Authorship
MM and HB developed the idea for the project and designed the study. ER
and AS executed the literature review and ER takes full responsibility
for the papers used and references. ER drafted the manuscript with
inputs and critical discussion from AS. MM and HB reviewed the
manuscript once it was completed for any changes or improvements. The
final version has been approved by all authors.
Details of Ethical Approval
Since this was a literature review, no specific ethical approval was
required.
Funding
No specific funding was sought for this study.
Bibliography
1. Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernandez-Diaz
S, et al. Medication use during pregnancy, with particular focus on
prescription drugs: 1976-2008. Am J Obstet Gynecol. 2011;205(1):51 e1-8.
2. Daw JR, Hanley GE, Greyson DL, Morgan SG. Prescription drug use
during pregnancy in developed countries: a systematic review.
Pharmacoepidemiol Drug Saf. 2011;20(9):895-902.
3. Engeland A, Bramness JG, Daltveit AK, Ronning M, Skurtveit S, Furu K.
Prescription drug use among fathers and mothers before and during
pregnancy. A population-based cohort study of 106,000 pregnancies in
Norway 2004-2006. Br J Clin Pharmacol. 2008;65(5):653-60.
4. Tinker SC, Broussard CS, Frey MT, Gilboa SM. Prevalence of
prescription medication use among non-pregnant women of childbearing age
and pregnant women in the United States: NHANES, 1999-2006. Matern Child
Health J. 2015;19(5):1097-106.
5. Fertiity treatment 2017. London: HFEA; 2019.
6. Fertility Treatment 2014 - 2016. Trends and Figures. London: Human
Fertilisation and Embryology Authority; 2018 April.
7. Ghosh K. Birth Characteristics in England and Wales: 2017. In:
Statistics OfN, editor. London2019.
8. Gaboon NEA. Recurrent Spontaneous Abortion: An Overview of Genetic
Backgrounds and Impact of Male Factors: A Review. International Journal
of Human Genetics. 2013;13(2):79-83.
9. Ibrahim Y, Johnstone E. The male contribution to recurrent pregnancy
loss. Transl Androl Urol. 2018;7(Suppl 3):S317-S27.
10. Flynn RW, MacDonald TM, Morris AD, Jung RT, Leese GP. The thyroid
epidemiology, audit, and research study: thyroid dysfunction in the
general population. J Clin Endocrinol Metab. 2004;89(8):3879-84.
11. Coton SJ, Nazareth I, Petersen I. A cohort study of trends in the
prevalence of pregestational diabetes in pregnancy recorded in UK
general practice between 1995 and 2012. BMJ Open. 2016;6(1):e009494.
12. Klerk C. The Psychological Impact of IVF Treatment. 2008.
13. Excellence. NIfHaC. Depression in adults: recognition and management
[Internet]. (Clinical guideline [CG90]) [Internet]. 2009
[updated 2016 Apr]. Available from:
https://www.nice.org.uk/guidance/cg90/resources/depression-in-adults-recognition-and-management-pdf-975742638037.
14. Grigoriadis S, Vonderporten EH, Mamisashvili L, Tomlinson G, Dennis
CL, Koren G, et al. Prenatal exposure to antidepressants and persistent
pulmonary hypertension of the newborn: systematic review and
meta-analysis. BMJ. 2014;348:f6932.
15. Jones SCM, L. Prescribing antidepressants in pregnant women. British
Journal of Family Medicine. 2014 Sept;2.
16. Cesta CE, Viktorin A, Olsson H, Johansson V, Sjolander A, Bergh C,
et al. Depression, anxiety, and antidepressant treatment in women:
association with in vitro fertilization outcome. Fertil Steril.
2016;105(6):1594-602 e3.
17. Friedman BE, Rogers JL, Shahine LK, Westphal LM, Lathi RB. Effect of
selective serotonin reuptake inhibitors on in vitro fertilization
outcome. Fertil Steril. 2009;92(4):1312-4.
18. Evans-Hoeker EA, Eisenberg E, Diamond MP, Legro RS, Alvero R,
Coutifaris C, et al. Major depression, antidepressant use, and male and
female fertility. Fertil Steril. 2018;109(5):879-87.
19. Klock SC, Sheinin S, Kazer R, Zhang X. A pilot study of the
relationship between selective serotonin reuptake inhibitors and in
vitro fertilization outcome. Fertil Steril. 2004;82(4):968-9.
20. Dooley M, Dineen T, Sarma K, Nolan A. The psychological impact of
infertility and fertility treatment on the male partner. Human
Fertility. 2014;17(3):203-9.
21. O’Connor E RR, Henninger M, et al. Screening for Depression in
Adults: An Updated Systematic Evidence Review for the U.S. Preventive
Services Task Force [Internet]. Rockville (MD): Agency for
Healthcare Research and Quality; 2016 Jan. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK349032/.
22. Use of Proton Pump Inhibitors (PPIs) In Pregnancy. In: England PH,
editor. London: UK Teratology Information Service; 2015 August.
23. Halfdanarson OO, Pottegard A, Bjornsson ES, Lund SH, Ogmundsdottir
MH, Steingrimsson E, et al. Proton-pump inhibitors among adults: a
nationwide drug-utilization study. Therap Adv Gastroenterol.
2018;11:1756284818777943.
24. Hvid-Jensen F, Nielsen RB, Pedersen L, Funch-Jensen P, Drewes AM,
Larsen FB, et al. Lifestyle factors among proton pump inhibitor users
and nonusers: a cross-sectional study in a population-based setting.
Clin Epidemiol. 2013;5:493-9.
25. Huijgen NA, de Ridder MA, Verhamme KM, Dohle GR, Vanrolleghem AM,
Sturkenboom MC, et al. Are proton-pump inhibitors harmful for the semen
quality of men in couples who are planning pregnancy? Fertil Steril.
2016;106(7):1666-72 e2.
26. Keihani S, Craig JR, Zhang C, Presson AP, Myers JB, Brant WO, et al.
Proton-pump inhibitor use does not affect semen quality in subfertile
men. Asian J Androl. 2018;20(3):290-3.
27. Excellence NIfHaC. Diabetes in pregnancy: management from
preconception to the postnatal period [Internet]. London: NiCE; 2015
Aug.
28. Jackson RA, Hawa MI, Jaspan JB, Sim BM, Disilvio L, Featherbe D, et
al. Mechanism of metformin action in non-insulin-dependent diabetes.
Diabetes. 1987;36(5):632-40.
29. Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH.
Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone,
D-chiro-inositol) for women with polycystic ovary syndrome, oligo
amenorrhoea and subfertility. Cochrane Database Syst Rev.
2017;11:CD003053.
30. Use of metformin in pregnancy [Internet]. In: England PH,
editor. London: UK Teratology Information Service; 2017 September.
31. Kim C-H, Lee, K.-H., Kwon, S.-K., Min, J.-Y., Ahn, J.-W., Kang,
B.-M. The comparison of the effect on IVF results of metformin and
insulin used during IVF cycles of infertile women with overt diabetes.
Fertil Steril. 2013;100(3):S327.
32. Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Macedo CR.
Metformin treatment before and during IVF or ICSI in women with
polycystic ovary syndrome. Cochrane Database Syst Rev.
2014(11):CD006105.
33. Jefferys A, Vanderpump M, Yasmin E. Thyroid dysfunction and
reproductive health. The Obstetrician & Gynaecologist.
2015;17(1):39-45.
34. Virta L, Eskelinen S. Prevalence of hypothyroidism in Finland—a
nationwide prescription study. European Journal of Clinical
Pharmacology. 2011;67(1):73-7.
35. Souter I, Batsis M, Petrozza J, Karmon A. Are Levothyroxine-Treated
Women with Hypothyroidism at Increased Risk for IVF Failure and Adverse
Pregnancy Outcomes? Fertility and Sterility. 2014;101(2):e18-e9.
36. 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.
37. Kim C-H, Ahn J-W, Kang SP, Kim S-H, Chae H-D, Kang B-M. Effect of
levothyroxine treatment on in vitro fertilization and pregnancy outcome
in infertile women with subclinical hypothyroidism undergoing in vitro
fertilization/intracytoplasmic sperm injection. Fertility and Sterility.
2011;95(5):1650-4.
38. Pelliccione F, Lania A, Pizzocaro A, Cafaro L, Negri L, Morenghi E,
et al. Levothyroxine supplementation on assisted reproduction technology
(ART) outcomes in women with subtle hypothyroidism: a retrospective
study. Gynecological Endocrinology. 2018;34(12):1053-8.
39. Dhillon-Smith RK, Middleton LJ, Sunner KK, Cheed V, Baker K,
Farrell-Carver S, et al. Levothyroxine in Women with Thyroid Peroxidase
Antibodies before Conception. N Engl J Med. 2019;380(14):1316-25.
40. Seungdamrong A. The Impact and Management of Subclinical
Hypothyroidism for Improving Reproductive Outcomes such as Fertility and
Miscarriage. Semin Reprod Med. 2016;34(6):331-6.
41. Elzbieta E-K, Pallav E. Thyroid function in male infertility.
Frontiers in Endocrinology. 2013;4.
42. Excellence NIfHaC. Hypertension in Pregnancy [Internet]. London:
NICE; 2019 Aug.
43. Go SA, Mozaffarian LD, Roger JV, Benjamin DE, Berry BJ, Borden MW,
et al. Heart Disease and Stroke Statistics—2013 Update: A Report From
the American Heart Association. Circulation. 2013;127(1):e6-e245.
44. Guo D, Li S, Behr B, Eisenberg ML. Hypertension and Male Fertility.
World J Mens Health. 2017;35(2):59-64.
45. Lu L, Sanchez X, Look C, Lacsamana J, Macanas E, Krey L. Prescribed
medications and sperm production and function during IVF. Fertility and
Sterility. 2002;78:S232-S3.
46. Guo D, Li S, Behr B, Eisenberg M. THE IMPACT OF HYPERTENSION AND
ANTIHYPERTENSIVES ON SEMEN QUALITY. Journal Of Urology.
2015;193(4):E1117-E.
47. Anderson HR. Prevalence of asthma. BMJ. 2005;330(7499):1037-8.
48. Garne E, Hansen AV, Morris J, Zaupper L, Addor M-C, Barisic I, et
al. Use of asthma medication during pregnancy and risk of specific
congenital anomalies: A European case-malformed control study. The
Journal of Allergy and Clinical Immunology. 2015;136(6):1496-502.e7.
49. Beau AB, Didier A, Lacroix I, Hurault-Delarue C, Montastruc J,
Damase-Michel C. Asthma medications during pregnancy: a cohort study in
EFEMERIS. Fundamental & Clinical Pharmacology. 2015;29:13-4.
50. Eltonsy S, Kettani F-Z, Blais L. Beta2-agonists use during pregnancy
and perinatal outcomes: A systematic review. Respiratory Medicine.
2014;108(1):9-33.
51. Alsaad D, Lindow S, Lee BH, Tarannum A, Abdulrouf PV. Maternal,
fetal, and neonatal outcomes associated with long‐term use of
corticosteroids during pregnancy. Obstetrician & Gynaecologist.
2019;21(2):117-25.
52. Use of inhaled corticosteroids in pregnancy [Internet]. In:
England PH, editor. London: UK Teratology Information Service; 2016
December.
53. Galambosi PJ, Kaaja RJ, Stefanovic V, Ulander V-M. Safety of
low-molecular-weight heparin during pregnancy: a retrospective
controlled cohort study. European Journal of Obstetrics and Gynecology.
2012;163(2):154-9.
54. Statistics OfN. Suicides in the UK: 2018 registrations. London: ONS;
2019.
55. Draper ESG, I. D. Kurinczuk, J. J. Smith, P. W. Boby, T. Smith, L.
K. et al. . UK Perinatal Deaths for Births from January to December
2017. Leicester: University of Leicester.; 2019 Oct.