Obstetrics & Gynaecology
Hurstville Private Hospital GP Bulletin
February - March 2019
In the first instance, infertility is only diagnosed when a couple (heterosexual) has not achieved conception after one year of regular, unprotected sexual intercourse. The age at diagnosis also plays a role, with couples where the women is aged 35 years and over, diagnosed as having infertility within six months of regular, unprotected sex.1
The cause of infertility can of course exist with either partner. Female infertility accounts for roughly one third of cases, male infertility for another third, with the remaining third attributed to combined male and female fertility issues.2
It is also important to distinguish between infertility and sterility. Sterility is diagnosed when there is no sperm production or any ovulation at all. In these instances it is not possible for conception using gametes from both parents to occur. Statistics for sterility are difficult to quantify and are multifactorial, however, between 8% to 12% of couples will experience infertility.1
The most common causes of female infertility include ovulatory concerns, fallopian tube or uterine damage and problems with the cervix.
In both females and males, age is becoming a key concern in infertility with many couples starting families later in life, well into their thirties and beyond. It has long been recognised a woman’s natural fertility decreases with age, however, IVF clinics continue to report age-onset decreased sperm viability and function, with a recent international study showing sperm counts have actually halved in the last 40 years.3
Polycystic Ovary Syndrome (PCOS) and endocrine disorders
PCOS is the most common hormonal cause of infertility. It is also a leading cause of Type 2 diabetes and is associated with dysregulation of glucose homeostasis.4
Around 12 – 21% of girls and women of reproductive age will present with PCOS5 although even in this day and age, the greater majority of women with PCOS (70%) remain undiagnosed.5
The cause of PCOS is not fully understood, however, recent genome-wide association studies have shown genetic links to metabolic and reproductive features of PCOS.4
PCOS characteristics include:
- Hyperandrogenism including hirsutism or male pattern alopecia and raised FAI or free testosterone,
- ovulatory dysfunction including oligomenorrhea or amenorrhea, and,
- polycystic ovarian morphology.
Different clinical diagnostic criteria and the broadness of symptoms make diagnosis difficult. Women may also present with different symptoms at different stages of life.
In general, at least two of the PCOS characteristics must be present for diagnosis. Younger women will present with reproductive symptoms in most situations (excluding obesity), while metabolic features will be more prevalent in older cases. Nevertheless, hyperandrogenaemia and insulin resistance remain the pathophysiological features of PCOS. With metformin, the most common treatment for insulin resistance in PCOS women, used to improve menstrual regularity.
Other endocrine pathologies that may cause infertility can be attributed to functional, physiological or organic causes and as such can be inherited or acquired.
These include:
- autoimmune hyperthyroidism (of which Graves’ Disease is the most common) and hypothyroidism – leading to anovulatory cycle, luteal phase defects, hyperprolactinaemia and sex hormone imbalance
- hypothalamic infertility from hypogonadotropic hypogonadism – resulting in little or no ovarian or testicular stimulation due to lack of gonadotropin-releasing hormone (GnRH), follicle stimulating hormone (FSH) and luteinising hormone (LH)
- pituitary tumours such as acromegaly and Cushing’s disease
- primary ovarian insufficiency or premature ovarian failure (loss of ovarian function before 40 years)
- endocrine effects of anorexia nervosa or bulimia nervosa
- obesity, separate to its link with PCOS
- lifestyle factors such as smoking, alcohol, illicit drug use, stress and excessive exercising.
Tubal, cervical and uterine factors
Of the non-hormonal causes of infertility, abnormal fallopian tubes, tubal blockages, cervical and uterine factors are the most common seen in clinical practice.
Tubal damage typically occurs following pelvic inflammatory disease caused by sexually transmitted infections such as Chlamydia trachomatis and Neisseria gonorrhoea.6 Tubal damage has also been linked to pelvic adhesions post surgery and chronic inflammation resulting from endometrioid tissue.6
Endometriosis affects more than 30% of women with infertility.7 It is characterised by growth outside of the uterus, including the pelvic cavity, fallopian tubes and ovaries.6 The associated inflammation and scaring can damage both sperm and ova as well as disrupt implantation.
The precise impact of uterine fibroids (leiomyomas or myomas) on infertility remains unknown however fibroids and cervical factors are thought to affect implantation or sperm passage to the fallopian tubes through benign growth or modified mucosal film.6
Other, rarer causes of non-hormonal infertility in women include chronic conditions, presence of uterine polyps, previous complications of pregnancy such as ectopic pregnancy and rare, acquired or inherited conditions.
Male infertility
About 2% of men have abnormal sperm paramaters.1 The three key parameters we assess include oligospermia, or low sperm count, which is responsible for 90% of male infertility, asthenospermia, or poor sperm motility, and teratospermia, or abnormal sperm morphology.1
Azoospermia, the complete absence of sperm, is often classed together with oligospermia, which is defined more appropriately as <15million sperm per mL
Abnormal semen including semen volume also contributes to male infertility and there is a positive association between abnormal sperm parameters and sperm count.1
Nevertheless male infertility can result from a range of conditions.
These include:
- genetic, such as Y-chromosome microdeletions and Klinefelter syndrome
- systemic disease and chronic conditions including Cushing’s syndrome and diabetes
- hypogonandotrophic hypogonadism or hyperprolactinaemia
- neurological or spinal chord injury
- infections and trauma
- ejaculatory disorders including ejaculatory disruption or retrograde ejaculation
- varicocele
- anti-sperm antibodies
- hypogonandotrophic hypogonadism or hyperprolactinaemia
- cancer, radiation and chemotherapy
- other pharmacological
- iatrogenic including vasectomy, injury to the vas deferens or other surgery
- lifestyle and environmental including, weight, smoking, alcohol and drug use.
Of particular interest is the recent increasing use of anabolic steroids among young men, which is becoming one of the main causes of preventable male infertility. Excessive anabolic steroid use can lead to irreversible infertility or at best take up to 12 months post use for sperm production to return to normal levels.
Current sperm assessment paramaters:1
- Volume 1.5ml
- Sperm concentration 15 million per mL
- Total sperm number 39 million per ejaculate
- Morphology 4% normal forms
- Vitality 58% live
- Progressive motility 32%
- Total motility 40%
Treatment includes:
IVF, ICSI and gonadotrophin medication.
Unexplained infertility
10 to 15% of those couples who need to proceed to IVF will have unexplained or idiopathic infertility. Unexplained infertility is usually denoted to female cases while idiopathic is reserved for male cases. In these instances the root cause of infertility cannot be determined, although some research has shown high sperm damage can explain the majority of idiopathic infertility.10 Management typically centres on the duration of infertility and age of the female partner. Initially couples will be commenced on expectant management followed by OI - ovulation induction, IUI - intrauterine insemination and finally IVF.
GPs need to conduct an initial consultation where they review medical and fertility history, assess general health, organise fertility tests, a GP referral - where under 35 refer at 12 months and over 35 refer at 6 months. These are tests that are typically requested for both females and males.
Female pre-treatment tests typically requested are:
- Rubella IgG
- Varicella zoster IgG
- Hepatitis B and Hepatitis C
- Chlamdia (IgG) and Chlamydia RNA (swab or urine)
- Gonorrhoea RNA (swab or urine)
- TSH (Thyroid Stimulating Hormone)
- TFT (Thyroid Function Tests)
- TPPA (Syphilis)
- Full Blood Count
- Blood group and antibodies
- AMH (Anti Mullerian Hormone)
- Pelvic TV scan - sonohysterogram
- HSG or Hy Co Sy (checking tubal patency).
Male pre-treatment tests typically requested are:
- Hepatitis B and Hepatitis C
- Chlamdia (IgG) and Chlamydia RNA (swab or urine)
- Gonorrhoea RNA (swab or urine)
- HIV
- TPPA (Syphilis)
- Full Blood Count
- Blood group and antibodies
- Semen analysis.
Dr Samen is an accredited Specialist Obstetrician and Gynaecologist. She has been practicing as a specialist for more than 20 years. Her specialist interests include Obstetrics, infertility, recurrent miscarriages and PCOS.
Dr Samen completed her Masters in Reproductive Medicine at the University of NSW in 2010, training extensively in Reproductive Medicine at Westmead and St George Hospitals, Sydney. She undertook her first medical degree in Iraq prior to commencing her specialist training in Obstetrics and Gynaecology. Following her move to Australia, Dr Samen trained at The Mater Mothers’ Hospital, Brisbane, and, Liverpool Hospital, Sydney, where she gained her fellowship.
Dr Samen is a fellow of the Arab Board of Obstetricians and Gynaecologists and speaks fluent Arabic and Turkish.
CONTACT DETAILS
T (02) 9646 5546
105B Harrow Road
Auburn, NSW, 2144
drwafasamen.com.au
References:
1. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. 2015 Oct-Dec:8(4):191-196. doi: 10.4103/0974-1208.170370.
2. How Common is Infertility? National Institutes of Health 2018.US Department of Health and Human Services. Available at https://www.nichd.nih.gov/heal... [accessed Jan 2019].
3. Levine H et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Human Reproduction Update 2017 Nov;23(6):646-659. https://doi.org/10.1093/humupd/dmx022.
4. Day F et al. Large-scale genome-side meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnostic criteria. PLOS Genetics 2018. Available at https://journals.plos.org/plos... [accessed Jan 2019].
5. March WA et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010;25:544–51.
6. Silvestris E et al. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol 2018;16:22. doi: 10.1186/s12958-018-0336-z.
7. Ciarmela P et al. Pathogenesis of Endometriosis and Uterine Fibroids. Editorial. Obstetrics and Gynecology International Vol 2013. Article ID 656571. http://dx.doi.org/10/1155/2013/656571.
8. Van Hamont D et al. Abnormal cervical cytology in women eligible for IVF. Human Reproduction 2006 Sept; 21(9):2359-2363. https://doi.org/10.1093/humrep/del132.
9. Low Sperm Count. Facts National Health Service UK. Available at https://www.nhs.uk/conditions/... [accessed Jan 2019]. Simon L et al. Sperm DNA damage has a negative association with live birth rates after IVF. Reprod Biomed Online 2013 Jan;25(1):68-78. doi:https://doi.org/10.1016/j.rbmo.2012.09.019.