18 Narmada Katakam, Ruth Arnesen, Caroline Watkins, Bert Stewart, and Luciano G. Nardo More than 80% of couples conceive in the first year and circa 90% in the second year, with some age dependent differences (Dunson et al. 2004). The remaining couples may require some kind of fertility treatment to achieve a successful pregnancy (te Velde et al. 2000; Taylor 2003a). Since 1991, 170 000 babies have been born as a result of in vitro fertilization (IVF) treatment in the UK, constituting almost 2% of all the newborns in the country (Human Fertilisation and Embryology Authority 2011). Infertility affects one in seven heterosexual couples in the UK, which equates to approximately 3.5 million people (Human Fertilisation and Embryology Authority 2010). These patients should be offered further clinical assessment and tailored investigations. However, earlier referral should be offered when the woman is aged 35 or over and there is a known cause or predisposing factor increasing the risk of infertility. Main reasons for infertility in the UK include male factors (30%), ovulation disorders (25%), unexplained (25%), tubal damage (20%), uterine or peritoneal factors (10%), and both male and female factors (40%). Some couples may have more than one cause (NICE 2013). Other reasons include uterine abnormality, endometrial factors, gamete or embryo defects, and pelvic conditions such as endometriosis, fibroids, and adhesions. Fertility assessments fail to identify an abnormality in up to 25% of infertile couples (Gelbaya et al. 2014). The number of couples seeking help for fertility is constantly rising. Women delaying starting a family until their late 30s or even early 40s is a significant contributing factor to the changing face of fertility performance in developing countries. The rate of spontaneous pregnancy amongst subfertile couples is less than the fertile population. Heterosexual couples should be seen together as the process affects both partners. Assessment should take individual needs, underlying medical problems, and treatment preferences into account. The patients should be given adequate information to be able to make well‐informed decisions about their management. Thorough assessment is recommended, to include history, clinical examination, and investigations (Kamel 2010) as outlined in Figure 18.1 and 18.2. Counseling is also an important part of the fertility assessment and should be offered to all patients seeking fertility treatment. Figure 18.1 Flow diagram outlining initial assessment of the female patient including clinical history, physical examination, and screening. AFC, antral follicle count; AMH, anti‐Müllerian hormone; FSH, follicle‐stimulating hormone; HSG, hysterosalpingogram; HyCoSy, hysterosalpingo‐contrast‐sonography; IVF, in vitro fertilization; Lap & Dye, laparoscopy and dye test; LH, luteinizing hormone; PRL, prolactin level; TFT, thyroid function test; TVUSS, transvaginal ultrasound scan. Figure 18.2 Flow diagram outlining initial assessment of the male patient including semen analysis. FSH, follicle‐stimulating hormone; ICSI, intracytoplasmic sperm injection; LH, luteinizing hormone; PRL, prolactin level; SSR, surgical sperm retrieval. General factors that reduce fertility in a couple include (Taylor 2003b): As shown in Table 18.1, the causes of female infertility can be mainly subdivided into ovulatory disorders, tubal and peritoneal factors, cervical factors, and unexplained causes (Sanders and Debuse 2003). Detailed history from both partners usually indicates the underlying reproductive problem (Forti and Krausz 1998; Whitman‐Elia and Baxley 2001; Case 2003; Taylor 2003b). History taking should include details of age, duration of infertility, cervical smears, breast changes and milk‐like discharge (galactorrhoea), excessive hair growth with or without acne, hot flushes, recent weight loss or weight gain, and previous fertility treatment. Table 18.1 Causes of and influences on female subfertility (Saunders and Debuse 2003). Reducing the body weight in women with a BMI of >30 kg/m2 may restore ovulation spontaneously, improve response to ovulation induction agents, and have a positive impact on pregnancy outcome. Using drugs such as clomifene citrate or metformin, or a combination of the above, can induce ovulation (see Table 18.2). Table 18.2 Ovulatory Disorders (WHO 1973). FSH, follicle‐stimulating hormone; LH, luteinizing hormone. Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders affecting women of reproductive age. It is an inherited condition with a prevalence of around 10%. Polycystic ovaries are seen on the scan in 20% of women investigated for infertility (Elsheikh and Murphy 2008). PCOS accounts for approximately 75% of women who suffer from infertility due to anovulation. The precise cause of PCOS remains unknown, but it is thought to be a thecal cell defect in androgen biosynthesis (Johnson 2007). In PCOS, luteinizing hormone (LH) is raised and follicle‐stimulating hormone (FSH) may be normal. This differentiates PCOS from secondary ovarian failure and early menopausal onset where both LH and FSH are raised. Women with PCOS have two to three times the normal number of preantral follicles, which arrest at the early antral stage. There is no dominant follicle. Other aetiologies should be excluded (congenital adrenal hyperplasia, androgen‐secreting tumours, Cushing’s syndrome). The 2003 Rotterdam Consensus Workshop revised the diagnostic criteria for PCOS to include two out of three of the following (Rotterdam Consensus 2004): Premature ovarian failure (POF) is amenorrhoea before the age of 40 without obvious cause. POF is characterized by amenorrhoea, hypo‐oestrogenism, and elevated gonadotropins. The incidence is 1% (Coulam et al. 1986; Shelling 2010). Causes of premature ovarian failure include: In POF, there is loss of fertility either due to the absence of follicles or lack of response to ovarian stimulation. There is sporadic ovulation and successful pregnancy in 5–10% of patients; however, this response cannot be reliably predicted. Clinical examination of both partners is essential. In some cases, a provisional diagnosis is usually possible by the end of the examination. Investigations are then performed to confirm the clinical diagnosis and exclude any abnormalities (ESHRE Capri Workshop Group 2004; Jose‐Miller et al. 2007; Macaluso et al. 2010). It is not always possible to assess the cause of infertility from history taking and clinical examination alone. No treatment should be commenced until basic investigations are performed and results reviewed. Investigations should be arranged after 12 months of trying to conceive. However, in women over 35 years old or in the presence of obvious identifiable reproductive problems, investigations should be arranged without delay.
Assessing the Infertile Couple
Introduction
Definitions
Epidemiology of Infertility
History Taking: Female Partner
Causes of Female Subfertlity
Influenced Or Caused By
Ovulatory factors
Tubal and peritoneal factors
Cervical factors
Ovulation Disorders
Group
Cause/Presentation
Hormones
WHO Group 1
Amenorrhoea
Hypothalamic–pituitary failure
No oestrogen
No/low FSH or LH
Normal prolactin
<1% infertility patients
WHO Group 2
Amenorrhoea/ oligomenorrhoea
Hypothalamic–pituitary dysfunction
Oestrogen present
FSH and LH levels – variable from cycle to cycle
Normal prolactin
Mostly PCOS
Elevated LH levels in PCOS
WHO Group 3
Amenorrhoea
Ovarianfailure
No oestrogen
Raised LH and FSH
History Taking: Male Partner
Clinical Examination
Clinical Examination: Female Partner
Clinical Examination: Male Partner
Investigations of an Infertile Couple
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