Regitz‐Zagrosek V, Roos‐Hesselink JW, Bauersachs J, Blomström‐Lundqvist C, Cífková R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA, ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy: The Task Force for the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC); EHJ 2018; 39:3165–3241.
7 7 Gibson P, Narous M, Firoz T, et al. Incidence of myocardial infarction in pregnancy: a systematic review and meta‐analysis of population‐based studies. Eur Heart J Qual Care Clin Outcomes. 2017; 3(3):198–207. doi:10.1093/ehjqcco/qcw060
8 8 Bush N, Nelson‐Piercy C, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M. Myocardial infarction in pregnancy and postpartum in the UK. Eur J Prev Cardiol 2013; 20:12–20.
9 9 Elkayam U, Goland S, Pieper PG, Silverside CK. High‐risk cardiac disease in pregnancy: Part i. J Am Coll Cardiol 2016; 68:396–410.
10 10 Mandalenakis Z, Rosengren A, Skoglund K, Lappas G, Eriksson P, Dellborg M. Survivorship in children and young adults with congenital heart disease in Sweden. JAMA Intern Med 2017; 177:224–230.
11 11 Presbitero P, Somerville J, Stone S, Aruta E, Spiegelhalter D, Rabajoli F. Pregnancy in cyanotic congenital heart disease. Outcome of mother and fetus. Circulation 1994; 89:2673–2676.
12 12 Van Tintelen JP, Pieper PG, Van Spaendonck‐Zwarts KY, Van Den Berg MP. Pregnancy, cardiomyopathies, and genetics. Cardiovasc Res 2014; 101:571–578.
13 13 Grewal J, Siu SC, Ross HJ, Mason J, Balint OH, Sermer M, Colman JM, Silversides CK. Pregnancy outcomes in women with dilated cardiomyopathy. J Am Coll Cardiol 2009; 55:45–52.
14 14 Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JPIII, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TMIII, Thomas JD. 2014 AHA/ACC guideline for the management of patients with valvular heart disease. J Am Coll Cardiol 2014; 63:e57–e185.
15 15 van Hagen IM, Thorne SA, Taha N, Youssef G, Elnagar A, Gabriel H, ElRakshy Y, Iung B, Johnson MR, Hall R, Roos‐Hesselink JW, ROPAC Investigators, EORP Team. Pregnancy outcomes in women with rheumatic mitral valve disease: Results from the Registry of Pregnancy and Cardiac Disease. Circulation 2018; 137:806–816.
16 16 Vause S, Clarke B, Tower CL, Hay C, Knight M. Pregnancy outcomes in women with mechanical prosthetic heart valves: A prospective descriptive population based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system. BJOG 2017; 124:1411–1419.
17 17 van Hagen IM, Roos‐Hesselink JW, Ruys TP, Merz WM, Goland S, Gabriel H, Lelonek M, Trojnarska O, Al Mahmeed WA, Balint HO, Ashour Z, Baumgartner H, Boersma E, Johnson MR, Hall R. Pregnancy in women with a mechanical heart valve: Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation 2015; 132:132–142.
12 The patient with diabetes
Mohammed A. Khan1,2, Neelam Potdar3, and Justin C. Konje1,2
1 Women’s Clinical Management Group, Sidra Medicine, Doha, Qatar
2 Weill Cornell Medicine-Qatar, Doha, Qata
3 Women’s Hospital, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester, UK
Case History 1: A 30‐year‐old woman with primary infertility of 3 years and previous failed attempts at intrauterine insemination (IUI) was reviewed for IVF treatment. She was known to have type 1 diabetes. Her body mass index (BMI) was 24 kg/m2 and HbA1c 12%. Her partner had normal semen analysis. She was referred to the endocrinologist for tighter glycemic control, following which IVF treatment was commenced. On the day of oocyte retrieval her fasting blood sugar was 10 mmol/L and her HbA1c was 8%. The serum estradiol level before oocyte retrieval was 10,120 pmol/L and 12 oocytes were retrieved, of which nine fertilized. She complained of abdominal bloating, nausea and a smelly vaginal discharge from day 5 after the retrieval.
Case History 2: A 39‐year‐old male with type 2 diabetes on oral hypoglycemics and prophylactic simvastatin presented to the assisted conception clinic. His BMI was 36 kg/m2 and semen analysis showed severe oligozoospermia. His complaints were reduced libido, mild erectile dysfunction (ED) and constant fatigue. Physical examination was normal and repeat semen analysis confirmed oligozoospermia. His HbA1c was 9% at presentation, serum FSH 3.4 IU/L, LH 4 IU/L, testosterone 3 nmol/L; karyotype and cystic fibrosis screening were normal. Investigations for the female partner were all normal.
Background
In general, patients undergoing assisted reproduction techniques (ART) are healthy individuals, but due to a rise in the prevalence of diabetes mellitus and impaired glucose tolerance globally over recent decades [1], it is not uncommon to see more and more diabetic couples seeking ART. For those providing ART, managing such couples is challenging, especially if the patient has type 1 or poorly controlled diabetes.
In animals, studies have shown that (a) diabetes is associated with ovarian atrophy, poor follicular development, impaired steroidogenesis and reduced progesterone levels [2], and (b) insulin administration corrects impairment of in‐vitro oocyte maturation and early pre‐embryonic development [3]. In women with well‐controlled type 1 (insulin dependent) diabetes, response to gonadotropin stimulation, fertilization and cleavage rates have been shown to be the same as those in women without diabetes [4,5]. The follicular fluid milieu in patients with well‐controlled type 1 diabetes is almost the same as in women without diabetes, except for the absence of epidermal growth factor.
In males, type 2 diabetes is known to be associated with reduced testosterone levels secondary to insulin resistance [6]. Although sex hormone binding globulin (SHBG) level is low with insulin resistance, the free testosterone level has been shown to be low in one‐third of men with diabetes [7]. Clinically, this could present as hypogonadism with symptoms and biochemical evidence of testosterone deficiency.
Management options
The metabolic derangements in diabetes do not only have teratogenic effects during the period of organogenesis but may also program the offspring’s future risk of cardiovascular and metabolic disease [8]. The risks of miscarriage, congenital malformations and perinatal mortality are three times higher in women with poor control compared against women with optimal glycemic control [9]. Whatever the management options considered; all these risks must be taken into consideration.
Female with diabetes
For those known to have diabetes, preconception care and counseling (PCC) aim to optimize the woman’s physical, social and emotional wellbeing preconceptually, to ensure healthy intra‐uterine environment for the developing fetus [10]. This has been shown to significantly reduce the risk of major and minor congenital anomalies in women with established diabetes mellitus [11], hence is the most important management step for a patient with diabetes planning to conceive through ART. There is great consistency in international guidelines on preconception care for the patients with diabetes especially on recommendations such as multidisciplinary approach involving social health professionals and counselors, optimal preconception HbA1c of between 6–7 %, medication review with respect to feto‐maternal safety profile, commencing high dose (5mg daily) folic acid, screening and management of diabetic complications and advising appropriate contraception until optimal metabolic control is achieved [12]. In Case History 1 with a high HbA1c of 12%, the woman requires referral to the multidisciplinary team for optimization of her glycemic control and preconception counseling as per international guideline recommendations in order to reduce the risk of adverse feto‐maternal outcomes.
Ovarian hyperstimulation syndrome (OHSS) should always be ruled out in any symptomatic woman who