Monday, 29 October 2012

INFERTILITY: Investigations and Management in the 21st century


Written by - Dr Lateef Akinola MSc, PhD, MBA, MRCOG
Consultant Gynecologist & Fertility / IVF Specialist


INFERTILITY is defined as the inability of a woman of reproductive age to get pregnant after ONE YEAR of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility. It affects about 1 in 6 couples. The incidence is about 10% to 15%, that is about 80 million couples are affected worldwide. Known causes of infertility is probably equally distributed among the male and female population.

Infertility is associated with negative stigma, stress and often brings about family disharmony. There are two types: PRIMARY INFERTILITY meaning that a woman has never been able to conceive and SECONDARY INFERTILITY where she has conceived at least once; with the pregnancy she either has children, miscarriages or she had terminations. Infertility treatment, across the world is very expensive, and largely not affordable by many patients especially in low-resourced areas of the world including Africa, Asia and other parts of the world.

Presently, it is not advised for a woman to wait for ONE year or more in the presence of pelvic infections, anovulation, polycystic ovaries syndrome, menstrual irregularities, and endometriosis or in women with age over 35 years. Also prompt fertility investigations and treatments are advised if the man have low sperm count and other sperm abnormalities, impotence, un-descended testes and spermatic duct blockages.

Causes of infertility
Among the infertile couples, a third of infertility causes can be attributed to the man, another third to the woman and the last third could be due to combination of factors (attributable to both sexes), undefined or unexplained and other causes like old age especially in the female, overweight/obesity or chronic medical diseases (diabetes, tuberculosis poor dieting). Notable causes of infertility in the females includes fibroid, infections /sexually transmitted diseases (Chlamydia and gonorrhea for example), blocked tubes, endometriosis and in the males associated causes includes low sperm count, abnormally shaped sperm or absence of sperm in the seminal fluid. The man could also be impotent, have retrograde ejaculation or have blocked spermatic cord from past sexually transmitted infections.

Stress and infertility
Infertility is often associated with an unacceptable level of personal stress that could manifest physically, and may be directed towards others at home, work and within or outside the family. Stress affects couple’s relationship, reduces libido and frequency of sexual intercourse. It also brings along ill health which can worsens infertility and can also diminish success rates after fertility treatment. There are a number of stress reducing processes out there that are acceptable and can be tried. These include acupuncture, yoga, physical exercise and herbal therapies to reduce stress, boost fertility and thereby improve treatment successes. Of importance to note, is the fact that some of the research evidence to support these therapies is neither robust nor evidence-based.

Infertility: Principles of Care & Counseling
Infertility counseling is a process during which a trained fertility counselor explains and assists patients to explore and understand what is happening to them in relation to their infertility. It is a useful process to allay the psychological effects of fertility problems, and to give adequate and effective evidence-based information in clear and concise ways. The methods of communications could be verbal, written and audio visual, to help the couples make informed decisions about fertility treatments as required. The counselor and the patient often develop a mutual bond and understanding which enable the patient to gain insight into his/her clinical situation regarding infertility. Also the causal/associated factors specific to the patient and her partner are explored in details. The counselor offers needed supports and empathy. During the counseling process, mutually acceptable, workable and reasonable routes to solutions are discussed including necessary details, which may be followed by the patients. All these will be in a non-judgmental and non-directive manner.

Initial detailed evaluation for husband and wife
An adage says it takes two to tango, therefore, needless to say that during the counseling and clinical evaluation the couples should be seen together. It is essential during the initial and subsequent clinical evaluations that the couple seeking fertility treatment should give relevant, factual and succinct information that will be documented and will help the fertility doctor to proffer appropriate treatment modalities for the couple. The couple must be reassured that all information given and obtained will be kept in absolute CONFIDENCE. The determinants of success following fertility treatments includes younger age, previous history of pregnancy or successful fertility treatments, little or no associated medical diseases, normal physical weight. Others include the cause and of course the duration of infertility. A woman younger than 35 years of age, with a normal body weight, with previous history of one or more spontaneous pregnancies, children or successful fertility treatments and without any confounding fertility impairing medical conditions (like endometriosis, fibroids and chronic anovulation/polycystic ovarian syndrome) are more successful than a woman that is older, with one or more fertility-impairing diseases, obese and has never been pregnant before.

Therefore, some pertinent questions and enquiries from the fertility specialist to answer will include:
1.       How many years the couple has been trying for baby?
2.       Information on menstrual cycle, sexual activities and contraceptive use
3.       Information on previous pregnancies\outcomes and fertility treatments (if any)
4.       Information on medical diseases and surgical \ Gynecological operations
5.       Any previous sexually transmitted infections (and treatments received)
6.       Is the female partner current with her Pap smear?
7.     The male\female partners’ personal or family history of cancer – breast, ovarian and testicular will be asked.
8.  Answers to important lifestyle inquiries like DRUGS intake (past/present), SMOKING, ALCOHOL, OCCUPATION and DIET should be confidentially disclosed to aid treatment planning.
9.       In addition, information on personal and family history of high blood pressure, diabetes; inherited family diseases of the brain, ovaries, uterus (womb) and others are essential and should also be documented.

It is pertinent to carry out complete general physical examination including the genital organs on the wife and husband. The chest (heart, breathing, and breast) and the abdomen examined for pain e.g. infections & swellings e.g. fibroids. The height and weight of the individuals will be measured to calculate the basal body mass index (BMI). The optimum BMI lies between 19 – 25 kg/m2. Laboratory investigations – for the female and male couples will include:

MALE
Semen analysis will be done to exclude any cause of abnormal or low sperm count in the man. A minimum value for a normal semen analysis (WHO, 2010) will have a volume of about 1.5 ml (1.4–1.7) a sperm concentration of about 15 million per ml (12–16) therefore, a total sperm number of about 39 million per ejaculate (33–46). The progressive motility percent of the sperm cells will be about 32% (31–34), their vitality percent around 58% live (55–63) and morphologically normal forms within 4.0% (3.0–4.0). Causes of sperm abnormalities include genetic (Klinefelter’s syndrome, Sertoli cell syndrome), Undescended testes, varicocele, infection (tuberculosis, gonorrhea, Mumps), prescribed or recreational drugs, poisons, scrotal heat and sometimes unknown. Others causes of male infertility like diabetes, impotence and stress are not uncommon. Therefore, the male partner should be screened for these and for infections. Hormonal and/or genetic should not be left out, if required. Treatments for any cause of sperm abnormalities are given as necessary usually by consultants in the specialties of Andrology, genetics and reproductive endocrinology, either alone or combined.

FEMALE
An assessment of the ovarian reserve and evidence for ovulation with blood tests are essential. Presently, serum Anti Mullerian Hormone (AMH), Prolactin and Day 21 Progesterone are measured. Nowadays, this is what I usually do for my group of patients. AMH (is independent of the menstrual cycle and can be done at any time of the cycle) is now widely recommended to assess ovarian reserve; it is evidently reported to be better than the routine measure of ovarian reserve using serum level of follicle stimulating hormone (FSH) which fluctuates widely and is dependent on the day of the menstrual cycle. Other hormonal, genetic and laboratory investigations for the woman will be as required and now depend on her clinical findings and situations. A pelvic ultrasound scans to count egg-containing follicles and rule out ovarian (cysts), uterine (fibroids) and other pelvic diseases e.g. tubal abscess or hydrosalphinges is also necessary and will be done. Other important investigations for the female partner will include screening for infections (HIV, syphilis, hepatitis and chlamydia); assessing for tubal patency with Hydrosonograms HyCoSy or Hysterosalpingogram (HSG); and for uterine abnormalities. If necessary and depending on the clinical findings a surgical evaluation and treatment of the woman including laparoscopic (abdomen/pelvic) and/or Hysteroscopic (uterine) examinations are done.

What is NEW, USEFUL and ADVISED include appropriate LIFE-STYLE practices such as

1.  AVOIDANCE of EXCESSIVE DRINKING of ALCOHOL in both females and males. For women not more than 1 – 2 units/week of alcohol and for men not more than 2 - 4 units/week of alcohol are recommended.
2.   It is recommended that couples should KEEP AWAY FROM SMOKING (which has detrimental fertility effects.
3.    Limit Coffee, Tea, Cola and Chocolate consumption.
4.    Maintenance of normal body weight, and avoidance of excessively low body weight & obesity (normal range of BMI 19 – 30 should be maintained). No surprise that women with significant anorexia nervosa and bulimia can have problems to conceive, because (in most cases) they have extremely low body weight for their age groups.
5.   NO tight underwear or pants for men
6.  Avoidance of testicular exposure to heat especially in such occupations involving prolonged bicycle\motorcycle rides, long distance lorry drivers and bakers.
7.   Avoid unnecessary exposures to X-rays, heavy metals and pesticides.
8.   Avoid DRUGS with adverse consequences on fertility especially over-the-counter and recreational drugs like cannabis, heroin and cocaine.
9.   Engage in sensible use of VITAMINS & MINERALS – A, B, C, D, E, Zinc, Selenium, Folic acid.
10. Endeavor to eat Balanced DIET & Fruits
11. Engage in moderate physical exercise to keep your BMI within the normal range at around 19 to 25 kg/meter square.


Couples are advised to engage in sexual intercourse every 2 to 3 days to significantly optimize their chance of pregnancy. The rituals of timing sexual intercourse to coincide with exact ovulation time can be very stressful and not recommended. Neither is that of keeping a daily basal body temperature chart throughout the year, more especially in the tropical environment like ours Africa\other parts of the world, where daily temperatures can be over 30 degrees easily. The use of urinary LH kits to determine fertile or ovulatory periods is expensive, often not accurate and can be confusing.

Management of male infertility will depend on the history and the clinical findings.
Abnormal semen quality (for example when the man has no sperm at all or has low count) can necessitate appropriate referrals to consultant specialists in Andrology, reproductive endocrinology and infertility. In some instances hormonal treatments may be recommended. A number of fertility treatment modalities like SPERM DONATION and\or RETRIEVAL of HUSBAND SPERM from the testicular organs like percutaneous epidydimal sperm aspiration (PESA) and testicular sperm aspiration (TESA) are available for in-vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) into the female eggs. In spermatic tubal or ductal obstructions, testicular disease with low or no sperm in the ejaculates, PESA and\or TESA techniques in combination with ICSI are very useful. Infections are treated with appropriate antibiotics.

Life style modifications like eating balanced diet and using diet supplements and vitamins are useful. In Varicoele; surgical treatment is presently controversial as there is currently no robust evidence to support surgical treatments even though this is widely practiced. In men with retrograde ejaculations of sperm into their urine (for example those having chronic diabetes), there are a number of effective methods for sperm harvesting from the urine immediately after sexual intercourse. The harvested sperm can be used successfully for fertility treatments. Impotence has several arrays of causal factors most especially including psychological, stress induced and in chronic medical conditions like diabetes. Some of these conditions are treatable with success using appropriately recommended specialist drugs like Viagra and other mechanical methods of causing sustained penal erection and to effect ejaculation in order to obtain sperm samples for fertility treatments. Occasionally, and as required, especially in difficult cases referrals for psychosexual therapies are essential part of treatments to overcome impotence.

Management of female infertility will also depend on clinical findings
Life- style activities e.g. smoking and alcohol drinking deteriorates fertility and reduces success in fertility treatments, these should be stopped or at most significantly curtailed for fertility potential amelioration and to improve successes of treatments given. Obesity is increasing in most societies. The health and social costs\consequences of obesity to the individual, family and the society are enormous. Fertility treatment success are limited and successful pregnancies risks includes higher risks of operative deliveries, wound infection, postpartum hemorrhage, prolonged risk of immobility and Venous Thrombo-Embolism (VTE). Obesity is often associated with Polycystic Ovarian Syndrome (PCOS), subfertility, advanced maternal age, diabetes and hypertension\preeclampsia with greater adverse maternal risks of pregnancy and post-delivery. The patients are strongly encouraged to get involved in better/effective weight reduction strategies (including modifications of diet as advised by a qualified dietician and engagement in physical exercise in moderation) to keep the BMI within the normal range to improve treatment successes (Norman et al., 2004, Sacks et al., 2009).

Maternal age
The optimal female reproductive age in women is estimated to be between 19-25yrs. There is increasing trend in voluntary age-related infertility as a result of postponement of childbirth by a significant proportion of women of reproductive age for career development, gains and economic empowerment. The consequences of this situation are obvious. Older women have higher risks of infertility (as infertility increases with advancing age) and exponential decline in egg quality and quantity. Furthermore, the chances of requiring IVF to conceive are significantly higher compared to younger women in the age bracket 20-30 years and IVF treatments are associated with increased failures. Fertility treatments including IVF, egg and embryo cryopreservation/storage, egg donation and surrogacy are not the panacea to age-related decline in egg numbers, quality or associated fertility problems later in life. Therefore, women are advised not to unnecessarily delay child-bearing to avoid future dissatisfactions and disappointments of unrealized fertility dreams and potentials.

Paternal age: Males are also not left out, as recent research publications have also linked advanced male age to declining male fertility, higher chance of sperm DNA fragmentation, increased risk of aneuploidies and congenital anomalies in offspring.

Adjuvant therapies (AT) and fertility
Adjuvant therapies are supplementary treatments given to women and men undergoing fertility treatments with the aim of increasing pregnancy and live births (Weiss et al., 2011). These therapies includes acupuncture, dietary supplements, multivitamins, steroids, aspirin, anticoagulants like heparin, various hormonal drugs (growth hormones, male hormones - DHEA) and Viagra. The benefits and cost-effectiveness of most of these drugs (aside from their high expense) are highly controversial. Therefore, for these reasons, the use of AT are neither recommended nor widely practiced and any usage should be clinically monitored and successes should be published to guide future uses. Ovulation disorders are amenable to treatment with essential hormonal drugs including clomiphene citrate tablets and injections of sex steroid hormones. These are prescriptions drugs that should be prescribed and usage monitored during fertility treatments by specialists only. They are associated with life threatening complications like ovarian hyper stimulation syndrome and multiple/higher order pregnancies. The medications can be used during monitored ovulation inductions with timed sexual intercourse or artificial insemination with husband or donor sperm; and in IVF / ICSI treatment cycles. Artificial insemination of sperm into the womb is indicated in women with treatable ovulation disorders and\or unexplained infertility. It is NOT recommended for women with tubal blockage and in men with moderate to severe sperm abnormalities or men with no sperm at all.

Women with fallopian tubal blockage are treated with either tubal microsurgery or IVF. It is noteworthy, that recent evidence points to the fact that IVF processes appears more cost-effective and more successes are recorded with IVF compared to tubal microsurgery. In older women with significantly reduced egg reserve EGG DONATION in combination with IVF is an acceptable treatment option. This should be supported with strong DONOR POLICIES and CONSENT procedures to prevent avoidable legal landmines. For those women with womb (uterus) diseases (fibroid, Asherman syndrome, and congenital abnormally shaped womb) effective corrective surgeries are available. Reproductive age women with functional ovaries, in whom the womb has been surgically removed womb for treatment of cancer or other diseases and in untreatable Asherman syndrome and in very rare congenital absence of the womb (Rokitansky syndrome) IVF (using own/donor eggs ad applicable) and SURROGACY are options to consider. For now, there are no internationally agreed surrogacy laws. Surrogacy affords opportunities for patients without a functional or congenitally absent womb and in those repeated implantation failures to have children. The process is fraught with significant emotional, social, moral, ethical, religious and legal problems and controversies. It is, therefore, highly important to give appropriate counseling before, during and after contractual surrogacy. This is to prevent lasting and permanent psychological and emotional scarring to the contractual partners and the children born through surrogacy.

When do we offer IVF? IVF is best offered when indicated only. It can be done for MALE factors including abnormally low or absence of sperm in ejaculates, after 3-4 failed artificial inseminations and for FEMALE factors, notably fallopian tubal blockage, ovulation disorders, unknown cause, repeated reproductive failures and in egg donation. In combination with pre-implantation genetic diagnosis, IVF becomes very useful in couples with repeated reproductive and/or implantation failures, sex-selection and in most women of advanced reproductive age up to and above 37 years of age. Of special mention is the fact that through the world, using the IVF processes, about 5 million live births have been reported so far and in Nigeria it is estimated that about 4,000 live births per year are delivered. Recent technology and equipment advancements in IVF processes, drugs, and IVF expertise have led to better outcomes and live births. The live birth rate has increased significantly now and is up to 50% or more in well-established fertility clinics like ours. Furthermore, pre-implantation genetic diagnosis (PGD) and Array Comparative Genomic Hybridization (aCGH) are available for used to detect genetically abnormal embryos before intrauterine transfer. By analyzing genetic composition of cells biopsied from embryos PGD and aCGH allow couples (especially with genetic abnormalities, repeated reproductive or implantation failures and those with advanced maternal age wishing to use own eggs) all of whom have high risk of having genetically disordered offspring to have a healthy child. PGD usage has even been extended to include HLA tissue-typing for 'savior siblings‘ in for example Fanconi’s anemia.

About the writer

Dr Lateef Akinola is a consultant member of the Royal College of Obstetricians & Gynecologists with full General Medical Council, UK and Nigerian Medical Council Specialist registration in obstetrics & gynecology.  He has several years’ experience and hands-on track record in all aspects of obstetrics and gynecology and specialization in reproductive medicine and surgery including fertility and IVF. He worked as a consultant at the Lincoln General Hospital and Luton and Dunstable hospitals in UK before joining The London Women’s Clinic (a renowned private IVF Centre, Harley street London). He is a member of the Society of Obstetrics and Gynecology of Nigeria, British Fertility Society, European Society of Human Reproduction and Embryology, and American Society for Reproductive Medicine. He has more than 30 publications in reputable scientific\medical journals to his credit. For more information on his services go to www.fertilityassyst.com, www.pregnancythinking.com, www.themedisonhospital.com

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