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While IVF itself is a complex and time-taking procedure, the process becomes more challenging for women with pre-existing medical conditions.
By Dr. Kaberi BanerjeeIVF in medically complicated patient
New reproductive technologies, such as in vitro fertilization (IVF), are becoming increasingly common, enabling infertile couples to become parents and create families. IVF is a complex series of procedures mostly involving many important steps including ovarian stimulation, oocyte retrieval and laboratory techniques to achieve maximal rates of fertilization and embryo development and embryo transfer (ET).
Medical conditions may affect the fertility of the female. Some medical conditions are aggravated due to IVF treatment and in some cases; pregnancy should not be carried for the benefit of the female partner, as it can compromise the life of the patient. The woman’s average age of marriage and childbearing is increasing, which further increases the chances of medical illnesses.
Hypertension is more frequent in ART-treated women as it increases the risk of placental complications, which appear to be compounded in ART versus unassisted pregnancies. Use of hormones in IVF for ovarian stimulation may affect the renin angiotensin aldosterone system involved in regulating blood pressure. These effects are prominent in hypertensive women seeking IVF treatment. Choice of antihypertensive medications is based on its efficacy, side effects and teratogenic potential. Antihypertensive medications such as Methyldopa and Labetalol are considered as safe to control blood pressure during IVF treatment. 1, 2, 3
Diabetes mellitus lowers the fertility by interfering with secretions of essential hypothalamic hormone called gonadotropin releasing hormone and luteinizing hormone in type 1 diabetes patients. Type-2 diabetic women are likely to develop polycystic ovarian syndrome (PCOS) which is characterized by obesity, increased testosterone, and infertility. Risk of congenital malformations in foetus is high in diabetic women. The goal of treatment in Type 1 & 2 diabetes mellitus is tight control of blood glucose levels and to adjust diet, exercise, metformin, and insulin to achieve tight control of carbohydrate metabolism. 4, 5, 6
Cardiovascular diseases such as coronary heart disease and comorbid conditions such as obesity, dyslipidemia, glucose intolerance and hypertension are common in infertile women particularly diagnosed with PCOS. In such patients, IVF treatment such as ovarian stimulation should be done in a controlled manner to avoid ovarian hyperstimulation syndrome which can be potentially life threatening. As pregnancy induces physiological changes in women, those with heart diseases need a thorough pre-pregnancy risk assessment and counselling, regular cardiology consultation, and surrogacy as an option, if the risk is high. 7, 8
Epilepsy is a common neurological disorder which can affect the fertility of a woman. Epilepsy and medications to treat it may affect the reproductive functions of hypothalamus – pituitary – ovarian axis causing elevation in Luteinizing hormone, low progesterone, and increased androgen. Epilepsy is also associated with hyposexuality, decreased libido and is commonly seen in PCOS patients. Neurologist fitness should be obtained before the IVF treatment. Standard protocol for ovarian stimulation should be used. However, prominent care must be taken to prevent the development of ovarian hyperstimulation syndrome (OHSS). If the patient is not fit (i.e. seizure episode less than 1 year) for the pregnancy, then surrogacy should be the option. Pregnant women with epileptic disease should consult neurologists for good seizure control and use of appropriate medication which are safe in pregnancy. 9, 10
Thromboembolism is a rare but life-threatening condition in IVF. Prophylaxis to prevent thrombosis is important particularly in women with a previous history of deep vein thromboembolism and above 40 years with thrombophilia. The risk of OHSS is also high in such patients. Medications such low molecular weight heparin, aspirin and compression stockings are commonly used for prophylaxis. 11, 12
Systemic Lupus Erythematosus (SLE)
SLE may affect fertility as women suffering from SLE may also face poor ovarian reserve and implantation failure due to autoimmune antibodies. Medications used to treat SLE such as cyclophosphamide may cause premature ovarian failure. Pre-pregnancy counselling is very important as women suffering SLE may have high risk of complications such as pregnancy induced hypertension, premature babies, stillbirth, renal damage and fetal abnormalities such as intrauterine growth restriction and neonatal death.
Regular rheumatologist visits for complete remission for at least two years is essential for starting IVF treatment. Controlled ovarian stimulation, use of donor eggs in case a patient is not fit for IVF hormonal injections, single embryo transfer, avoidance of OHSS, administration of co-adjuvant therapy and use of estrogen and progesterone through a non-oral route may constitute the safest approach. In very high-risk active cases (disease with significant organ impairment), surrogacy will be the best option. 13
Obesity is considered when body mass index (BMI) is more than 30 kg/m2. It affects fertility in women by causing disturbance in the hypothalamus-pituitary-ovarian axis, leading to hormonal imbalance. Obesity is also a common trait seen in women suffering with POCS in addition to other comorbid conditions such as hypertension, cardiovascular diseases, dyslipidaemia, and diabetes. Obesity in women may aggravate gallbladder diseases, asthma and osteoarthritis, high requirement of hormones in IVF and difficult instrumentation during procedures. Obesity impairs the response of women to assisted conception treatments leading to lower reproductive outcomes. 14, 15
Thyroid hormones directly affect reproductive hormones. Hypothyroidism and hyperthyroidism are common, important, and often reversible or preventable cause on infertility. Hypothyroidism is associated with decreased plasma concentrations of estrogens and androgens with deficient luteinizing hormone (LH) secretion. There may be reduced libido and anovulation. In hyperthyroidism, there may inadequate mid-cycle LH surges leading to anovulation. So, tight control of thyroid function is must for better reproductive outcomes. Levothyroxine for hypothyroid and propylthiouracil for hyperthyroid woman are recommended medications. 16
In recurrent IVF failure, thyroid antibodies screening should be done in euthyroid women and intravenous immunoglobulins can be given in positive cases (30). During IVF, HCG for ovulation should be very helpful to compensate for low LH levels. After embryo transfer, good luteal support should be given.
Hyperprolactinemia is a common endocrine cause of infertility. It lowers the fertility by inhibiting 5α-reductase activity and increases adrenal androgen secretion leading to the anovulation and also induces hyperinsulinemia. Use of medications such as cabergoline or bromocriptine help to reduce prolactin levels and improve IVF success rate. 17
In conclusion, the prior identification and preparation of the patient at increased risk of complications will enable the clinician to avoid problems in advance, anticipate the necessary management, and optimize outcomes.