History

Fact Explanation
Age of both partners Fertility rate in both males and females have shown to reduce with advanced age. Evaluation for subfertility should start early when the partners are older particularly if the woman is older than 35 years.[1][5][7][8]
Duration of subfertility This is important to diagnose presence of subfertility as the definition states, not being able to conceive after 1 year of unprotected vaginal sexual intercourse, in the absence of any known reproductive pathology.[1]
Methods used for contraception It is important to determine if the couple is on a long term contraceptive method such as subdermal implants or Intrauterine device so that it will have to be discontinued as there is expectations of pregnancy and that they are engaging in unprotected vaginal intercourse.[1][7][8]
Frequency of sexual intercourse In order to achieve conception the couple should engage in regular sexual intercourse so this factor has to be elicited during the history taking. 90% of fertile couples become pregnant within a year of regular intercourse. After two years, this rises to 95%.[1][7][8]
Menstrual history of the woman Presence of oligomenorrhoea, amenorrhoea may indicate a problem with hypothalamo pituitary ovarian axis. Women who are not ovulating may have variable cycle lengths, oligomenorrhoea, or amenorrhoea. Oligomenorrhoea or amenorrhoea can present as part of polycystic ovary syndrome.[1][6][7][8]
History of endometriosis/ adenomyosis Both these conditions are associated with female subfertility when they cause structural damage or adhesions.[1][6][7][8]
History of pelvic infections or sexually transmitted infections Subfertility is a long term complication of pelvic inflammatory disease (PID). Chlamydia and gonorrhoea are the major pathogens that cause pelvic inflammatory disease. If untreated, pelvic inflammatory disease can cause tubal factor subfertility. Bacterial vaginosis increases risk of PID and infertility in women. Trichomanas vaginalis can cause female tubal infertility and male infertility. Human papilloma virus infection can reduce sperm motility and induce abortion. Human immunodeficiency virus infection can reduce sperm quality[6][7][10][11]
Symptoms such as constipation, cold intolerance, heavy menstrual blood loss, lethargy,weight gain with reduced appetite etc May indicate presence of hypothyroidism which affects fertility.[7]
Symptoms such as diarrhea, heat intolerance, scanty or absent menstruation, weight loss with increased appetite etc May indicate presence of hyperthyroidism that can also affect fertility.[7]
History of previous pregnancies and their out come This is important in prognostication because a previous full term pregnancy is associated with a better chance of conception, either naturally or after treatment.[8][7][9]
History of erectile dysfunction or premature ejaculation in male and vaginismus or dysperunia in female These can affect the coital frequency in the couple and thus affect fertility.[2][7]
History of occupational heat or radiation exposure in males These can affect semen quality or cause oligospermia in males.[1][2][4][7]
History of mumps or measles in males These infections can cause orchitis and affect sperm production.[2][7]
History of testicular trauma, torsion of testes, undescended testes These may cause oligospermia or testicular failure.[2][7]
History of pelvic/ testicular/inguinal/scrotal/retroperitoneal surgery or irradiation or chemotherapy In females pelvic surgery can cause adhesions and tubal factor subfertility. In males this kind of surgery can cause ejaculatory dysfunction, vas deference obstruction etc. Irradiation and chemotherapy can cause gonadal failure [2][7]
Histroy of current or recent acute or chronic medical illnesses Recurrent respiratory infections may be the presentation of cilliary dysfunction syndromes such as Kartagener's syndrome that cause male infertility. Chronic infections, other endocrine disorders etc. can also reduce fertility.[2][7]
History regarding medication Anabolic steroids use can lead to hypogonadism. Medicines such as sulfasalazine, methotrexate, colchicine, cimetidine, spironolactone can affect fertility.[7]
Social history regarding smoking and alcohol consumption Smoking and alcohol consumption has shown to affect fertility. Smoking reduce fertility in women and reduce semen quality in men.Excess alcohol consumption during pregnancy is toxic to the fetus and excessive alcohol intake also reduce semen quality.[2][3][6][7]
Headache, blurred vision, visual field defects These can be the presenting symptoms of a pituitary adenoma.[2][7]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 20 Aug 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. PETER N. KOLETTIS, Evaluation of the Subfertile Man. Am Fam Physician.[online] 2003 May 15;67(10):2165-2172.[viewed on 19 Aug 2014] Available from; http://www.aafp.org/afp/2003/0515/p2165.html
  3. WDOWIAK A, SULIMA M, SADOWSKA M, GRZEGORZ B, BOJAR I. Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization. Ann Agric Environ Med [online] 2014, 21(2):450-3 [viewed 19 August 2014] Available from: doi:10.5604/1232-1966.1108623
  4. DE FLEURIAN G, PERRIN J, ECOCHARD R, DANTONY E, LANTEAUME A, ACHARD V, GRILLO JM, GUICHAOUA MR, BOTTA A, SARI-MINODIER I. Occupational exposures obtained by questionnaire in clinical practice and their association with semen quality. J Androl [online] 2009 Sep-Oct, 30(5):566-79 [viewed 20 August 2014] Available from: doi:10.2164/jandrol.108.005918
  5. KOCOURKOVA J, BURCIN B, KUCERA T. Demographic relevancy of increased use of assisted reproduction in European countries. Reprod Health [online] 2014 May 26:37 [viewed 20 August 2014] Available from: doi:10.1186/1742-4755-11-37
  6. ARYANPUR M, TARAHOMI M, SHARIFI H, HEYDARI G, HESSAMI Z, AKHOUNDI M, MASJEDI MR. Comparison of spermatozoa quality in male smokers and nonsmokers of Iranian infertile couples. Int J Fertil Steril [online] 2011 Oct, 5(3):152-7 [viewed 19 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25101159
  7. ALAINA B. JOSE-MILLER, JENNIFER W. BOYDEN, KEITH A. FREY. Infertility. Am Fam Physician.[online] 2007 Mar 15;75(6):849-856.[viewed on 20 Aug 2014] Available from; http://www.aafp.org/afp/2007/0315/p849.html
  8. CAHILL DJ, WARDLE PG. Management of infertility BMJ [online] 2002 Jul 6, 325(7354):28-32 [viewed 20 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123548
  9. TEMPLETON A, MORRIS JK, PARSLOW W. Factors that affect outcome of in-vitro fertilisation treatment. Lancet [online] 1996 Nov 23, 348(9039):1402-6 [viewed 21 August 2014] Available from: doi:10.1016/S0140-6736(96)05291-9
  10. ROHRBECK P. Pelvic inflammatory disease among female recruit trainees, active component, U.S. Armed Forces, 2002-2012. MSMR [online] 2013 Sep, 20(9):15-8 [viewed 22 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24093960
  11. APARI P, DE SOUSA JD, MüLLER V. Why Sexually Transmitted Infections Tend to Cause Infertility: An Evolutionary Hypothesis PLoS Pathog [online] , 10(8):e1004111 [viewed 22 August 2014] Available from: doi:10.1371/journal.ppat.1004111

Examination

Fact Explanation
Body mass index BMI over 30 and below 19 have shown to be associated with subfertility.[1]
Hirsutism in females Is a feature of poly cystic ovarian syndrome[2]
Secondary sexual characteristics Should be examined in order to diagnose genetic and endocrine problems that may cause subfertility[3]
Testicular position and volume Genital examination is important to determine presence of undescended testes, underdeveloped testis, testicular tumor impalpable vas deferens, varicocele, inguinal scars from unreported inguinal surgery etc that can lead to infertility in males[1][3]
Presence of vaginal/penile discharge This may indicate presence of sexually transmitted infection[1]
Size and characteristics of uterus and ovaries palpated abdominally and bimanually Determined to exclude presence of uterine and ovarian masses, normal uterine anatomy, endometritic nodules etc that can contribute to female subfertility[1]
Body habitus Alterations in the normal body habitus may indicate presence of endocrine disorders. Gynecomastia, galactorrhea may be observed in patients with pituitary adenomas. Tall males with other features such as gynecomastia, less muscular body, less facial and body hair etc may indicate Klinefelter syndrome[1][4]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 20 Aug 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. AQUINO CI, NORI SL. Complementary therapy in polycystic ovary syndrome. Transl Med UniSa [online] 2014 Apr:56-65 [viewed 20 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24809037
  3. PETER N. KOLETTIS, Evaluation of the Subfertile Man. Am Fam Physician.[online] 2003 May 15;67(10):2165-2172.[viewed on 19 Aug 2014] Available from; http://www.aafp.org/afp/2003/0515/p2165.html
  4. AKSGLAEDE L, JUUL A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol [online] 2013 Apr, 168(4):R67-76 [viewed 20 August 2014] Available from: doi:10.1530/EJE-12-0934

Differential Diagnoses

Fact Explanation
Sexually transmitted infection Can lead to subfertility in both males and females[1][5][6]
Endocrine disorders Disorders such as congenital adrenal hyper plasia, Cushing's syndrome, hyperthyroidism, hypothyroidism, pituitary ademona etc can cause subfertility[1][5][6]
Cryptorchidism Can cause oligospermia or testicular failure[1][5][6]
Klinefelter syndrome Causes infertility in males[4][5]
Endometriosis Causes subfertility in females[1][6]
Uterine fibroids Are associates with reduced fertility in females[3][6]
Polycystic ovarian syndrome(PCOS) Infertility is a clinical feature of PCOS among other features such as amenorrhea, oligomenorrhea, hirsutism, obesity, acne etc[2][6]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 20 Aug 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. AQUINO CI, NORI SL. Complementary therapy in polycystic ovary syndrome. Transl Med UniSa [online] 2014 Apr:56-65 [viewed 20 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24809037
  3. GUO XC, SEGARS JH. The impact and management of fibroids for fertility: an evidence-based approach. Obstet Gynecol Clin North Am [online] 2012 Dec, 39(4):521-33 [viewed 20 August 2014] Available from: doi:10.1016/j.ogc.2012.09.005
  4. AKSGLAEDE L, JUUL A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol [online] 2013 Apr, 168(4):R67-76 [viewed 20 August 2014] Available from: doi:10.1530/EJE-12-0934
  5. PETER N. KOLETTIS, Evaluation of the Subfertile Man. Am Fam Physician.[online] 2003 May 15;67(10):2165-2172.[viewed on 19 Aug 2014] Available from; http://www.aafp.org/afp/2003/0515/p2165.html
  6. ALAINA B. JOSE-MILLER, JENNIFER W. BOYDEN, KEITH A. FREY. Infertility. Am Fam Physician.[online] 2007 Mar 15;75(6):849-856.[viewed on 20 Aug 2014] Available from; http://www.aafp.org/afp/2007/0315/p849.html

Investigations - for Diagnosis

Fact Explanation
Seminal fluid analysis According to World Health Organization reference values semen volume should be 1.5 ml or more; pH 7.2 or more; sperm concentration 15 million spermatozoa per ml or more; total sperm number 39 million spermatozoa per ejaculate or more; total motility 40% or more motile, or progressive motility 32% or more; vitality 58% or more live spermatozoa and sperm morphology 4% or more normal forms. At least two semen samples should be tested at least two or three weeks apart before a diagnosis is made.[1][3][4][5]
Serum Follicular stimulating hormone level(FSH) Both high and low FSH levels may be associated with hypogonadism. High levels suggest gonadal failure. Low level may suggest presence of hypogonadotropic hypogonadism[1][3][4][3]
Serum luteinizing hormone level(LH) If serum LH level is raised, with a normal FSH level suggests PCOS. High LH level together with high FSH may suggest premature menopause (ovarian failure). Low levels of LH are common in women with eating disorders, female athletes, high levels of stress and disorders of the pituitary or hypothalamus. LH surge is required for ovulation. Therefore low LH levels result in anovulation and subfertility [1][3][4]
Serum testosterone level Low testosterone levels in men suggests presence of hypogonadism. If associated with Low FSH level can diagnose hypogonadotropic hypogonadism[1][3][4][5]
Serum prolactin level High prolactin levels inhibit secretion of FSH. Therefore, if your prolactin levels are high, ovulation is suppressed leading to infertility. High prolactin level warrants further investigations to rule out pituitary tumour.[1][3][4]
Serum Thyroid stimulating hormone level Done to rule out hypothyroidism or hyperthyroidism in symptomatic patients.[1][3][4]
Serum anti mullerian hormone level Is a good indicator of ovarian follicular reserve.[1][3][4]
Mid luteal progesterone assay Done to assess ovulation. A rise in the mid luteal level of progesterone suggest that ovulation has taken place.[1][3][4]
Transvaginal ultrasound scan Is a basic imaging test done in women to assess Fallopian tubes, uterus, and pelvis.[1][3][4]
Hysterosalpingogram Done to assess tubal patency in women to rule out tubal factor subfertility.[1][3][4]
Laparoscopy Is considered the gold standard to evaluate pelvic pathology in women.[1][2][3][4]
Scrotal ultrasound scan Done to detect varicocele, hydrocele, cysts. abacess, tumours etc[1][3][4][5]
Testicular biopsy Done to find cause for male infertility when a semen analysis suggests presence of abnormal sperms but hormone assays are normal. In some cases, sperm obtained from a testicular biopsy can be used for in vitro fertilization.[1][3][4][5]
Hysteroscopy Is done to visualize inside the uterus to rule out conditions such as congenital uterine anomalies, fibroids,polyps, uterine synechiae etc.[1][2][3][4]
Transrectal ultrasonography Can be performed to rule out ejaculatory duct obstruction[1][4][5]
Postejaculatory urinalysis Done in patients with a low volume of ejaculate, to rule out retrograde ejaculation[1][4][5]
Screen for sexually transmitted infections(STI) Should be done if STI are suspected[3][4][5]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 20 Aug 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. ZHANG E, ZHANG Y, FANG L, LI Q, GU J. Combined hysterolaparoscopy for the diagnosis of female infertility: a retrospective study of 132 patients in china. Mater Sociomed [online] 2014 Jun, 26(3):156-7 [viewed 20 August 2014] Available from: doi:10.5455/msm.2014.26.156-157
  3. ALAINA B. JOSE-MILLER, JENNIFER W. BOYDEN, KEITH A. FREY. Infertility. Am Fam Physician.[online] 2007 Mar 15;75(6):849-856.[viewed on 20 Aug 2014] Available from; http://www.aafp.org/afp/2007/0315/p849.html
  4. CAHILL DJ, WARDLE PG. Management of infertility BMJ [online] 2002 Jul 6, 325(7354):28-32 [viewed 20 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123548
  5. PETER N. KOLETTIS, Evaluation of the Subfertile Man. Am Fam Physician.[online] 2003 May 15;67(10):2165-2172.[viewed on 19 Aug 2014] Available from; http://www.aafp.org/afp/2003/0515/p2165.html

Investigations - Fitness for Management

Fact Explanation
Full blood count Done to exclude anemia in preparing for pregnancy.[1]
References
  1. CAHILL DJ, WARDLE PG. Management of infertility BMJ [online] 2002 Jul 6, 325(7354):28-32 [viewed 22 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123548

Management - General Measures

Fact Explanation
Weight control Has shown to improve fertility in both females and males. For women who have a BMI of 30 or above, losing weight is likely to increase their chance of conception and women who have a BMI of less than 19, increasing body weight is likely to improve their chance of conception. Men who have a BMI of 30 or above are likely to have reduced fertility.[1][4]
Smoking cessation Studies have shown that smoking reduce fertility in women and reduce semen quality in men.[1][2]
Limit alcohol consumption Excess alcohol consumption during pregnancy is toxic to the fetus so women should limit alcohol to 1 or 2 units once or twice per week and avoid episodes of intoxication. Excessive alcohol intake has shown to reduce semen quality.[1][3]
Preconceptional folate and councelling Women who are planning to conceive should take folic acid in order to prevent neural tube defects in the fetus. 0.4 mg daily is the required dose. But if there was a history of neural tube defect in a previous pregnancy the recommended dose is 5 mg.[1]
Avoid heat exposure at work, wearing tight under wear etc in males These measures are important because elevated scrotal temperature is shown to be associated with reduced semen quality,[1]
Advice on regular sexual intercourse Unprotected vaginal sexual intercourse at least 2-3 times in a week is required for a successful conception. The natural conception rate for couples who have regular unprotected sexual intercourse is shown to be over 90% in three years time.[1]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 20 Aug 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. ARYANPUR M, TARAHOMI M, SHARIFI H, HEYDARI G, HESSAMI Z, AKHOUNDI M, MASJEDI MR. Comparison of spermatozoa quality in male smokers and nonsmokers of Iranian infertile couples. Int J Fertil Steril [online] 2011 Oct, 5(3):152-7 [viewed 19 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25101159
  3. WDOWIAK A, SULIMA M, SADOWSKA M, GRZEGORZ B, BOJAR I. Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization. Ann Agric Environ Med [online] 2014, 21(2):450-3 [viewed 19 August 2014] Available from: doi:10.5604/1232-1966.1108623
  4. LEISEGANG K, BOUIC PJ, MENKVELD R, HENKEL RR. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort. Reprod Biol Endocrinol [online] 2014 May 7:34 [viewed 20 August 2014] Available from: doi:10.1186/1477-7827-12-34

Management - Specific Treatments

Fact Explanation
Ovulation induction Most commonly used agent is clomifene citrate. It is an anti-estrogen agent that occupies hypothalamic estrogen receptors and interrupy normal feed back mechanisms, increasing release of FSH. FSH stimulate ovaries to produce more follicles. Ovulation induction can also be done by laparoscopic ovarian drilling in cases of polycystic ovarian syndrome unresponsive to medical treatment.[1][5]
Intrauterine insemination A prepared small sample of sperm is introduced into the uterine cavity with a fine uterine catheter. Suitable for people with unexplained infertility, mild endometriosis or mild male factor infertility.[1][4]
In vitro fertilization(IVF) IVF treatment is offered to women with unexplained infertility who have not conceived after 2 years of regular unprotected sexual intercourse. Ovarian stimulation is done and eggs are collected under ultrasound guidance. These eggs are fertilized in a petri dish with sperm or intracytoplasmic sperm injection. The fertilized embryos are then transferred into uterine cavity. A pregnancy test is performed after 2 weeks to to confirm conception.[1][2][3]
Surgical treatment Surgical procedures such as laparoscopy for ablation of endometriosis, myomectomy for uterine fibroids, tubal surgery to relieve blocked Fallopian tubes etc are done to restore fertility.[1][6]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 20 Aug 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. ANIFANDIS G, MESSINI C, DAFOPOULOS K, SOTIRIOU S, MESSINIS I. Molecular and Cellular Mechanisms of Sperm-Oocyte Interactions Opinions Relative to in Vitro Fertilization (IVF). Int J Mol Sci [online] 2014 Jul 22, 15(7):12972-97 [viewed 20 August 2014] Available from: doi:10.3390/ijms150712972
  3. CHANG EM, SONG HS, LEE DR, LEE WS, YOON TK. In vitro maturation of human oocytes: Its role in infertility treatment and new possibilities. Clin Exp Reprod Med [online] 2014 Jun, 41(2):41-6 [viewed 20 August 2014] Available from: doi:10.5653/cerm.2014.41.2.41
  4. NIKBAKHT R, SAHARKHIZ N. The influence of sperm morphology, total motile sperm count of semen and the number of motile sperm inseminated in sperm samples on the success of intrauterine insemination. Int J Fertil Steril [online] 2011 Oct, 5(3):168-73 [viewed 20 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25101161
  5. ANGEL M, GHOSE S, GOWDA M. A randomized trial comparing the ovulation induction efficacy of clomiphene citrate and letrozole. J Nat Sci Biol Med [online] 2014 Jul, 5(2):450-2 [viewed 20 August 2014] Available from: doi:10.4103/0976-9668.136241
  6. GUO XC, SEGARS JH. The impact and management of fibroids for fertility: an evidence-based approach. Obstet Gynecol Clin North Am [online] 2012 Dec, 39(4):521-33 [viewed 20 August 2014] Available from: doi:10.1016/j.ogc.2012.09.005