History

Fact Explanation
Duration of subfertility subfertility is diagnosed when a couple is not being able to conceive after 1 year of unprotected vaginal sexual intercourse, in the absence of any known reproductive pathology. When the duration of subfertility increases, success rate of ART decreases.[1][5][6]
Age of partners Pregnancy rates decreases with increasing age thus the success of ART decreases with increasing age.[1][5][6]
Gynecologic history, including pelvic infections, sexually transmitted infections, menstrual cycle etc. Subfertility is a long term complication of pelvic inflammatory disease (PID). 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. Heavy menstruation, irregular menstrual bleeding etc. may represent an intrauterine fibroid, polyp, or synechiae. Secondary dysmenorrhea may indicate presence of endometriosis/ adenomyosis, which are associated with female subfertility when they cause structural damage or adhesions. Presence of oligomenorrhoea, amenorrhoea may indicate a problem with hypothalamo pituitary ovarian axis. These women may not be ovulating properly. Oligomenorrhoea or amenorrhoea can present as part of polycystic ovary syndrome also.[1][8][9]
Current and past medical/surgical problems Mumps or measles infection can cause orchitis and affect sperm production. Past pelvic/testicular/inguinal/scrotal/retroperitoneal surgery in males can cause ejaculatory dysfunction, vas deference obstruction etc. In females pelvic surgery can cause adhesions and tubal factor subfertility. Recurrent respiratory infections may be the presentation of cilliary dysfunction syndromes such as Kartagener's syndrome that cause male infertility. Chronic infections, diseases, other endocrine disorders etc. can also reduce fertility.[1][8][9]
Contraceptive usage 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.[1][8][9]
Prior pregnancies from either partner and their outcome History of repetitive abortions, malpresentation during pregnancy, uterine surgery, postpartum uterine infections, retained products of conception, postpartum curettage etc in a female may indicate subfertility due to uterine problems. Previous successful pregnancy increases success of ART. If there are previous failed attempts of ART, the success of current attempts will also be low.[1][8][5][9]
Current and past medication history Anabolic steroids use can lead to hypogonadism. Medicines such as sulfasalazine, methotrexate, colchicine, cimetidine, spironolactone etc can affect fertility.[1][8][9]
Social history regarding smoking, alcohol consumption, drug use 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. Smoking is associated with low ART success. Intravenous drug abuse put the person at risk of developing infections such as HIV and hepatitis.[1][2][4]
Occupation and potential environmental exposure to chemicals/heat/radiation All these can affect semen quality or cause oligospermia in males. Irradiation and chemotherapy can cause gonadal failure.[1][3]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 3 Sep 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  2. 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 3 Sep 2014] Available from: doi:10.5604/1232-1966.1108623
  3. 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 2 Sep 2014] Available from: doi:10.2164/jandrol.108.005918
  4. 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 2 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25101159
  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 2 Sep 2014] Available from: doi:10.1186/1742-4755-11-37
  6. 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 2 Sep 2014] Available from: doi:10.1016/S0140-6736(96)05291-9
  7. 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 2 Sep 2014] Available from: doi:10.1371/journal.ppat.1004111
  8. ALAINA B. JOSE-MILLER, JENNIFER W. BOYDEN, KEITH A. FREY. Infertility. Am Fam Physician.[online] 2007 Mar 15;75(6):849-856.[viewed on 2 Sep 2014] Available from; http://www.aafp.org/afp/2007/0315/p849.html
  9. CAHILL DJ, WARDLE PG. Management of infertility BMJ [online] 2002 Jul 6, 325(7354):28-32 [viewed 2 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123548

Examination

Fact Explanation
Body mass index(BMI) BMI over 30 and below 19 have shown to be associated with subfertility. High BMI reduces the success rates of ART.[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]
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. eg; moon facies truncal obesity and striae, may be due to Cushing syndrome. 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 2 Sep 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 2 Sep 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 2 Sep 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 2 Sep 2014] Available from: doi:10.1530/EJE-12-0934

Investigations - for Diagnosis

Fact Explanation
Semen analysis Semen analysis is done to detect and evaluate male factor infertility. The male who undergoes the test should, abstain from coitus for 3-5 days prior to semen collection. The sample has to be analyzed within one hour of collection. The World Health Organization (WHO) has established normal reference values. Any abnormal study result should be confirmed with a repeat semen analysis. If results remain abnormal, other tests should be done to recognize the cause. If the ejaculate is of low volume, post-ejaculatory urinalysis should be done to rule out retrograde ejaculation.[1][3][4][5]
Serum Follicular stimulating hormone level(FSH) Done on cycle day 3 to evaluate ovarian function. Both high and low FSH levels may be associated with hypogonadism. High levels suggest gonadal failure. Low level may suggest presence of hypogonadotropic hypogonadism. If the FSH level is greater than 15 mIU/mL, the prognosis is poor. [1][3][4][3]
Clomiphene citrate challenge test This test can be done for patients >40 years or for in those suspected to have poor ovarian reserve . A dose of clomiphene citrate is administered on cycle days 5-9. Then estradiol and FSH levels are drawn on 3rd and 10th days after adminsistration. The results are considered abnormal if the 3rd or10th day FSH level >15 mIU/mL or the 3rd day estradiol level >75 pg/mL. The interpretation of this test is based on the fact that estrogen suppress FSH by a negative feedback mechanism and if the woman has an elevated 10th estradiol level due to clomiphene, but her FSH level is not suppressed, this implicates significant decrease of ovarian reserve.[6]
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 estradiol (E2) This is also a test for ovarian reserve. Usually done on cycle day 3. Estradiol level greater than 75 pg/mL, is associated with poor prognosis. [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.A deficiency in by the corpus luteal progesterone production has been attributed to infertility and recurrent pregnancy losses in women those who with otherwise unexplained miscarriages. This results must be a repetitive event to be a true cause of infertility or miscarriage. [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 in patients with unremarkable history or examination findings, to assess tubal anatomy and patency. Is usually performed 2-5 days after the cessation of menstrual flow. This test can also be used to evaluate the uterine cavity.[1][3][4]
Hysteroscopy Is done for direct visualization inside the uterine cavity to rule out conditions such as congenital uterine anomalies, fibroids,polyps, uterine synechiae etc. Should be done in women planning to undergo IVF. [1][2][3][4]
Laparoscopy Is considered the gold standard to evaluate pelvic pathology in women. All test including hysteroscopy and laparoscopy should be performed and be negative before diagnosis of unexplained infertility. [1][2][3][4]
Transrectal ultrasonography Can be performed to rule out ejaculatory duct obstruction. [1][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]
Screen for sexually transmitted infections(STI) Should be done if there is suspicion of the presence of STI. [3][4][5]
Screening for endocrine problems If there are clinical features of PCOS, androgen studies (total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxyprogesterone) should be performed. If there are clinical features of thyroid disease, a thyroid-stimulating hormone (TSH) test should be done. If there is galactorrhea or irregular menses, serum prolactin level should be measured. If diabetes is suspected, a glucose tolerance test or fasting blood sugar test should be done.[1][3][4]
Serum beta hCG Should be done two weeks after employing ART to diagnose pregnancy. [7]
References
  1. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 2 Sep 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 2 Sep 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 2 Sep 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 2 Sep 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 2 Sep 2014] Available from; http://www.aafp.org/afp/2003/0515/p2165.html
  6. MILEWICZ T, KRZYSIEK J, BLAKAłA B, KRZYCZKOWSKA-SENDRAKOWSKA M, RADOWICKI S, KACALSKA O, ZABIńSKA M. Clomiphene citrate challenge test and serum anti-Müllerian hormone levels in women with menstrual irregularities and/or infertility. Folia Histochem Cytobiol [online] 2007:S119-21 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18292818
  7. ANNAN JJ, GUDI A, BHIDE P, SHAH A, HOMBURG R. Biochemical Pregnancy During Assisted Conception: A Little Bit Pregnant J Clin Med Res [online] 2013 Aug, 5(4):269-274 [viewed 05 September 2014] Available from: doi:10.4021/jocmr1008w

Management - Specific Treatments

Fact Explanation
Intrauterine Insemination (IUI) This ART employs introduction of a prepared small sample of sperm into the uterine cavity via a fine uterine catheter just before release of ova/ovum in a natural or stimulated cycle. This method is used in the treatment of men with mild to moderate problems in sperm count and/or motility or retrograde ejaculation and also for treatment of women who have scarring or defects of the cervix, unexplained infertility, mild endometriosis. IUI may help in presence of antisperm antibodies in the female or male. IUI can be used in combination with medications that stimulate ovulation. This combination treatment increases the chance of pregnancy in some cases.[6][7][8][9]
In vitro fertilization(IVF) IVF may be considered in instances such as tubal disease, male factor subfertility, endometriosis, anovulation, reduced fecundity with advanced maternal age etc. A pregnancy test is done 2 weeks later to diagnose conception. Surplus embryos can be cryopreserved for future cycles. Risks related to IVF include ovarian hyperstimulation syndrome, first trimester venous thromboembolism, psychological stress, multiple gestations, operative risks. Use of leuprolide injection instead of hCG for final oocyte maturation has shown to reduce the incidence of ovarian hyperstimulation. Treating hyperstimulation with heparin thromboprophylaxis in the first trimester will lower the venous thromboembolism risk.[2][5][6][9]
intracytoplasmic sperm injection (ICSI) This technique is used in men with severely abnormal sperm parameters (together with IVF) or when fertilization has failed in IVF cycles. Men with severe oligozoospermia should have karyotyping and cystic fibrosis screening prior to ICSI. Sperms can be obtained from ejaculate or in case of azoospermia, retrieval is done by percutaneous acquisition or via open surgery. Intracytoplasmic morphologically selected sperm injection(IMSI), is a method where screening is used to select a spermatozoon for ICSI with an optimal shape. This gives a better clinical out come.[1][3][4]
Gamete intrafallopian transfer(GIFT) GIFT involves laparoscopic placement of eggs and sperm directly in the ampullary portion of the fallopian tube. So that in vivo fertilisation will occur at the natural site. Therefore can be used only in women who have at least one patent Fallopian tube. The patient undergoes controlled ovarian hyperstimulation. The oocytes are collected under ultrasonographic guidance by transvaginal approach. Afterwards 3-4 oocytes are placed laparoscopically along with sperm into one of the fallopian tubes.[10]
During zygote intrafallopian transfer (ZIFT) In this technique, oocytes are retrieved similar to IVF and GIFT and are allowed to fertilize in vitro as in IVF. After one day from fertilization i.e. the two cell stage 3-4 zygotes are transferred laparoscopically into one of the fallopian tubes. This procedure is termed tubal embryo transfer(TET) if the embryos are allowed to develop further.[10]
Donor insemination Is offered in cases of azoospermia, severe oligozoospermia, failed ICSI, risk of trnsmitting genetic disorders via male partner, women seeking pregnancy without a male partner etc. Donors are recruited by sperm banks. They are screened for a personal or family history of medical or genetic disorders and sexually transmitted. Blood group and karyotype are tested and a serology test for previous exposure to cytomegalovirus is done. The woman needs to have at least one functioning fallopian tube and she must ovulate either naturally or in response to stimulation. IUI is the method of sperm introduction.[6][9][10]
Egg donation Can be used when a woman who have primary ovary insufficiency (POI), secondary ovarian insufficiency, bilateral ovary agenesis, carriers of known genetic diseases, poor egg quality. An egg donor is screened as for sperm donors and undergoes ovary stimulation and egg retrieval steps of similar to IVF. The donated egg can then be fertilized by sperm from the woman's partner or other male, and the resulting embryo placed into the woman's uterus.[9][10]
Surrogates and Gestational Carriers This method is offered to women who are unable to carry a pregnancy to term or incapable of producing healthy eggs. A surrogate(Genetic surrogate) who is woman inseminated with sperm from the male partner of the couple, in which case The resulting child is biologically related to the surrogate and to the male partner. A gestational carrier(Gestational surrogate) is a woman implanted with an embryo produced with the gametes of the couple. This child will not be biologically related to her. Egg or sperm donation can also be used in this situation.[11][12]
References
  1. NERI QV, LEE B, ROSENWAKS Z, MACHACA K, PALERMO GD. Understanding fertilization through intracytoplasmic sperm injection (ICSI). Cell Calcium [online] 2014 Jan, 55(1):24-37 [viewed 04 September 2014] Available from: doi:10.1016/j.ceca.2013.10.006
  2. HARRISON EC, SCOTT TAYLOR JS. IVF Therapy for Unexplained Infertility. Am Fam Physician. [online] 2006 Jan 1;73(1):63-65.[viewed on 3 Sep 2014] Available from; http://www.aafp.org/afp/2006/0101/p63.html
  3. ESTEVES SANDROC, AGARWAL ASHOK. Re: Sperm retrieval rates and intracytoplasmic sperm injection outcomes for men with non-obstructive azoospermia and the health of resulting offspring. Asian J Androl [online] 2014 December [viewed 04 September 2014] Available from: doi:10.4103/1008-682X.127817
  4. ESTEVES SC, MIYAOKA R, OROSZ JE, AGARWAL A. An update on sperm retrieval techniques for azoospermic males Clinics (Sao Paulo) [online] 2013 Feb, 68(Suppl 1):99-110 [viewed 04 September 2014] Available from: doi:10.6061/clinics/2013(Sup01)11
  5. BAKER VL. Mild ovarian stimulation for in vitro fertilization: one perspective from the USA J Assist Reprod Genet [online] 2013 Feb, 30(2):197-202 [viewed 04 September 2014] Available from: doi:10.1007/s10815-013-9946-8
  6. Fertility. Assessment and treatment for people with fertility problems. NICE clinical guideline 156[online] Issued: February 2013.[viewed on 3 Sep 2014] Available from; http://www.nice.org.uk/guidance/cg156/resources/guidance-fertility-pdf
  7. KOYUN E, OKYAY RE, DOğAN ÖE, KOVALı M, DOğAN SS, GüLEKLI B. The effect of intrauterine insemination time on semen parameters J Turk Ger Gynecol Assoc [online] , 15(2):82-85 [viewed 05 September 2014] Available from: doi:10.5152/jtgga.2014.36776
  8. YAVUZ A, DEMIRCI O, SöZEN H, ULUDOğAN M. Predictive factors influencing pregnancy rates after intrauterine insemination. Iran J Reprod Med [online] 2013 Mar, 11(3):227-34 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24639750
  9. ROWELL P, BRAUDE P. Assisted conception. I--General principles. BMJ [online] 2003 Oct 4, 327(7418):799-801 [viewed 05 September 2014] Available from: doi:10.1136/bmj.327.7418.799
  10. TOURNAYE H, CAMUS M, UBALDI F, CLASEN K, VAN STEIRTEGHEM A, DEVROEY P. Tubal transfer: a forgotten ART? Is there still an important role for tubal transfer procedures? Hum Reprod [online] 1996 Sep, 11(9):1815-8 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8921040
  11. JADVA V, BLAKE L, CASEY P, GOLOMBOK S. Surrogacy families 10 years on: relationship with the surrogate, decisions over disclosure and children's understanding of their surrogacy origins Hum Reprod [online] 2012 Oct, 27(10):3008-3014 [viewed 05 September 2014] Available from: doi:10.1093/humrep/des273
  12. REILLY DR. Surrogate pregnancy: a guide for Canadian prenatal health care providers CMAJ [online] 2007 Feb 13, 176(4):483-485 [viewed 05 September 2014] Available from: doi:10.1503/cmaj.060696