Published on June 11, 2019
1. Diaa Mohammad Srahin 6th year Medical Student Al-Quds University Obstetrics & Gynecology December/ 2018 Hebron Governmental Hospital
2. Introduction A delay in conception is one of the commonest reasons that a woman will consult her doctor. There is no one universal definition of Subfertility, but the commonest accepted definition is a failure to conceive after 12 months of regular unprotected intercourse. The incidence of subfertility is thought to affect about one in seven heterosexual couples in UK.
3. Subfertility can be classified as : Primary, in couples who have never conceived. Secondary, in couples who have previously conceived. Subfertility Primary Secondary
4. The causes of subfertility can be Male causes. Female causes. Mixed. Subfertility Male causes Female causes Factors affect both sexes
5. Fecundability This is the likelihood of conception occurring with one cycle of appropriately timed mid-cycle intercourse. “ likelihood of conception after 1 month of mid-cyclic unprotected sex. “ With the female partner age of 20 years, the fecundity rate is 20%. By age 35 years, the rate drops to 10%. So the fecundity changes with the female age
6. What point dose the decline become significant ??? When passed 35 years it is significant
7. Natural conception Eggs are thought to be fertilizable for about 12–24 hours post-ovulation, while sperm can survive in the female reproductive tract for up to 72 hours. For a woman with a normal menstrual cycle of 28 days, ovulation occurs around day 14. The ‘Fertile window’ for women will, therefore, be different depending on the average length of their menstrual cycle (e.g. for a woman with a 28-day menstrual cycle, her optimal fertile window will be between days 12 and 15).
8. Epidemiologic figures 80% of couples achieve conception within 1 year. 25% within 1st month. 60% within 6 months. 75% within 9 months. 90% within 18 months.
9. Factors affecting the natural conception rate Age Female >35 years, due to decline in oocyte quality & number. Male age is also an important factor; semen quality tends to fall in men over the age of 50, while frequency of intercourse tends to fall in men over the age of40. Smoking reduces fertility in female & semen quality in males.
10. Cont. Alcohol harmful to the fetus & can affect sperm quality . Coital frequency stress & anxiety may affect libido & coital frequency & thus impact on fertility. Recommended coital frequency is two to three times per week. Body weight Over or under weight can affect ovulation. women with a body mass index (BMI) of >29 or < 19 will have difficulty conceiving.
11. Cont. Drugs non-steroidal anti-inflammatory drugs (inhibit ovulation). chemotherapy (destroys rapidly dividing cells e.g. gametes). cimetidine, sulphasalazine, androgen injections (affects sperm quality). Occupational hazards exposure to chemicals and radiation adversely affects male and female fertility.
12. Causes of subfertility The main causes of subfertility will vary in different countries. In the UK subfertility is caused by : A. 30% Male factors B. 30% Female factors. C. 25% Unexplained. D. 15% Both Male and Female or Other Causes.
13. Female causes of subfertility Female causes HPO axis dysfunction Ovarian factors Cervical Endometrial factors Tubal
14. ovulation Oogenesis occurs in the ovary from the 1st trimester of embryonic life and completed by 28-30 weeks of gestation. (7 million oocytes). The oocytes are arrested at the prophase stage of the 1st meiotic division. At birth, the oocyte pool reduced to 2 million. By menarche, 500,000 oocyte are present. The ovulatory process is initiated once the HPO axis matures and FSH and LH acquire their normal secretory pattern.
15. Ovarian problems 1. Central Pituitary insufficiency (trauma/ tumor/ congenital) Hypothalamic insufficiency Hyperprolactinemia (drug/ tumor/ empty sella) Luteal phase defect 2. Peripheral defects Gonadal dysgenesis Premature ovarian failure Ovarian tumor Ovarian resistance 3. Metabolic diseases. PCOS ( most common cause of anovulation) Thyroid Obesity Androgen excess (adrenal/ neoplastic)
16. The most common cause of anovulation is PCOS. Women with PCOS also suffer from menstrual irregularities (usually oligo- or amenorrhoea). increased hair growth (hirsutism), acne and are more commonly overweight. They also are at higher risk of diabetes and cardiovascular disorders.
17. The diagnosis of PCOS is based on a score of two out of three of the Rotterdam criteria
18. Marker of ovarian reserve In the ovary, anti-Müllerian hormone (AMH) is produced by the granulosa cells. AMH levels can be measured in blood and are shown to be proportional to the number of small antral follicles. In women, serum AMH levels decrease with age and are undetectable in the post-menopausal period. AMH levels represent the quantity of the ovarian follicle pool and are a useful marker of ovarian reserve. AMH measurement can also be useful in the prediction of the extremes of ovarian response to gonadotrophin stimulation for in vitro fertilization.
19. Cont. Female reproductive potential is directly proportionate to the remaining number of oocytes in the ovaries, which is called ovarian reserve. Ovarian reserve declines after the age of 35 in an average healthy woman, or at an earlier age due to genetic predisposition, surgery or following exposure to toxins, such as chemotherapy. The ovarian reserve can help to predict the response to ovarian stimulation in ART. The AFC seen on TVUSS is a good indicator of ovarian reserve (<4 predicting low response, >16 high response). Neither AMH nor AFC are perfect indicators and most clinics utilize both to assess ovarian reserve
20. Tubal blockage Causes: 1. previous PID such as chlamydia infection 2. Inflammatory process within the abdomen/pelvic cavity 3. Inflammatory process as a result of surgery or endometriosis => internal scares (adhesions). 4. History of ectopic pregnancy.
21. Endometrial factors Any abnormality in the endometrium may prevent successful implantation of embryo. Examples: Endometriosis (15% of infertile females have endometriosis) Uterine fibroids Adhesions. Polyps. Tubal ligation Can be surgically managed.
22. Uterine factors (less than 10%) Congenital malformations Submucosal fibroids Uterine polyps Asherman’s syndrome (adhesions and/or fibrosis of the endometrium particularly but can also affect the myometrium.)
23. Cervical factors Cervicitis Cervical stenosis Mullerian duct abnormalities Inadequate mucus production
24. History and PE Hx: Length of time spent trying for pregnancy. Any previous pregnancies. Coital frequency . Occupation. Menstrual history. Previous history of pelvic inflammatory disease . Previous medical and surgical history. Previous fertility treatment. Cervical smear history. General health – screen for history of thyroid disorders
25. Examination Signs of PCOS Thyroid disease signs Pelvic examination any uterine pathology such as fibroids Vaginal atrophy in POF Cervical stenosis & mucus General BP, pulse, height and weight
26. Investigations Check for ovarian reserve Check for HPO dysfunction. Check tubal patency: Hysterosalpingogram (HSG). Hysterocontrast synography (HyCoSy). Operative laparoscopy and dye test. HSG => radio-opaque dye => X-ray. HyCoSy => sono-opaque contrast =>ultrasound.
27. Hysterosalpingogram (HSG)
28. Hysterocontrast synography (HyCoSy)
29. Treatment Ovulation induction(OI): Clomifene Citrate (CC). Induce gonadotropin release by occupying the estrogen receptors in the hypothalamus, thereby interfering with the normal feedback mechanisms, increasing the release of FSH and stimulating the ovary to produce more follicles. 70% of women on CC will ovulate, with a pregnancy rate of 15–20%. There is a risk of multiple pregnancies (12%) &therefore women on CC should be monitored by us scans to track the growth of their follicles.
30. laparoscopic ovarian drilling (LOD) For unknown reasons, passing electrical energy through polycystic ovaries can result in the induction of ovulation. it is a surgical procedure, & it’s only appropriate to offer such treatment to who have not responded to CC. OI can also be performed by offering a small dose of FSH to induce follicular growth. It require follicular tracking with US scan to minimize the risk of multifollicular ovulation & risk of multiple pregnancy.
31. Intrauterine insemination (IUI): Performed by introducing a small sample of prepared sperm into the uterine cavity with a fine uterine catheter. This process usually requires mild stimulation with FSH to produce 2-3 mature follicles. Follicular tracking is essential to avoid over or under stimulation. The success rate of this procedure ranges between 15 and 20 percent in top fertility units.
32. In vitro fertilization (IVF): The success rate of IVF per cycle is about 30% in women <35 years of age. In essence, the ovaries are stimulated with FSH, and are encouraged to produce up to 8–10 follicles. Induction of ovulation is then performed with an injection of hCG, after which the eggs can be collected during an ultrasound guided procedure via a very fine needle. These eggs will be fertilized in a petri dish with sperm or, if required, the sperm can be injected directly into the egg (intracytoplasmic sperm injection, ICSI). When fertilization occurs, the fertilized embryo(s) is then replaced into the uterine cavity. Approximately 2 weeks after embryo transfer, a pregnancy test is performed to check for successful implantation.
33. Undergoing IVF does not preclude the patient from the normal complications of pregnancy, such as miscarriage or ectopic pregnancies. The risk of ectopic pregnancy for women who have undergone IVF is higher than for the general population, at 3–4 per cent. There is the added risk of overstimulating the ovaries during an IVF cycle. Patients with ovarian hyperstimulation syndrome (OHSS) present with ascites, hugely enlarged multifollicular ovaries, pulmonary edema, and are at risk of multiorgans failure and coagulopathy. These patients need to be admitted to hospital and managed under strict protocols under the care of specialist teams.
34. • Video
35. Surgical treatment Offered if there is tubal blockage or endometrial abnormality (polyp, adhesion or fibroid).
36. Causes Hypothalamic-pituitary disease Obesity Primary hypogonadism Sperm transport disorders Defective ejaculation
37. Gonadotropin-releasing hormone (GnRH) or gonadotropin deficiency. Hypogonadotropic hypogonadism Hypothalamic-pituitary disease
38. 1. Congenital idiopathic hypogonadotropic hypogonadism. Isolated gonadotropin deficiency resulting in eunuchoidism. Eunuchoidism Sexual infantilism Eunuchoid body Undeveloped sexual organsNo sexual hormones Hypothalamic-pituitary disease
39. 2. Acquired: Tumors: Pituitary macroadenomas e.g. macroprolactinomas and nonfunctioning adenomas. Infiltrative disease: sarcoidosis, tuberculosis, fungal infections. Vascular lesion: Pituitary infarction and carotid aneurysm. Hormonal: hyperprolactinemia, estrogen excess, glucocorticoid excess and androgen excess Hypothalamic-pituitary disease
40. 3. Drugs: Opioid-like. Central nervous system-acting drugs. Inhibit GnRH or gonadotropin secretion, resulting in secondary hypogonadism. GnRH analogues Suppress gonadotropin secretion, as in men with prostatic carcinoma 4. Systemic or chronic illness or chronic nutritional deficiency. Hypothalamic-pituitary disease
41. Obesity Associated with decrease in serum sex hormone binding globulin (SHBG). Low serum gonadotropin, total testosterone. Sperm quality may also be inversely related to BMI; > 25 Kg/m2 has lower motile cells.
42. Primary hypogonadism Testicular disorders hypergonadotropic hypogonadism. 1) Congenital disorders: - Klinefelter's syndrome: have very small testes and almost always have azoospermia. - Y chromosome related defects: microdeletions in the long arm. Testicular biopsies in these men may show germinal cell maturation arrest or Sertoli cell-only syndrome. - Cryptorchidism: failure of testes descent into the scrotum. - Defective androgen receptor or synthesis
43. Primary hypogonadism 2) Aquired disorders: - Varicoceles : dilatations of the pampiniform plexus of the spermatic veins in the scrotum. Infection: viral orchitis, especially mumps. Due to germinal cell damage, ischemia, or the immune response to the infection. - Drugs: alkylating agents like cyclophosphamide, antiandrogens, cimitidine. Through inhibiting testicular androgen production or action. - Radiation. - Hyperthermia. - Testicular cancer.
44. Sperm transport disorders The epididymis is an important site for sperm maturation. The vas deferens transports sperm from the epididymis to the urethra.
45. Defective ejaculation Spinal cord disease or trauma. Sympathectomy. Autonomic disease. Erectile dysfunction. Mechanical obstruction. Premature ejaculation.
46. History and PE History: Length of time spent trying for pregnancy. Fathered any previous pregnancies. History of mumps or measles History of testicular trauma, surgery to testis Occupation Medical and surgical history
47. Physical examination: Testicular examination : testicular volume, consistency, masses, absence of vas deferens, varicocele, evidence of surgical scars.
48. Investigations Semen analysis It should be performed after the patients have abstained from sexual intercourse for 3–4 days. Two abnormal test results are required to diagnose male subfertility. normal parameters for semen analysis (WHO criteria) Volume >1.5 ml pH >7.2 Sperm concentration >15 million/ml Total sperm number >39 million/ ejaculate Motility >50% grade a & b Morphology >30% normal forms
49. Semen analysis The WHO reference values for semen analysis: Semen volume: ≥1.5 mL Semen pH: ≥7.2 Sperm concentration: ≥15 million spermatozoa per mL Total sperm number: ≥39 million spermatozoa per ejaculate Total motility : ≥40% motile or Progressive motility: ≥32% Vitality: ≥58% live spermatozoa Sperm morphology (percentage of normal forms): 4%
50. Pathological findings Conditions Characteristics Aspermia No ejaculate Hypospermia Low ejaculate volume (< 1.5 mL) Azoospermia No spermatozoa in the ejaculate Cryptozoospermia < 1 million spermatozoa/mL of ejaculate Oligospermia < 15 million spermatozoa/mL of ejaculate Asthenozoospermia < 32% of spermatozoa show progressive motility (category PR) Teratozoospermia Increased amorphous spermatozoa Oligoasthenoteratozoospermia (OAT syndrome) Low concentration, insufficient motility, and increased amorphous spermatozoa
51. For men with a very low sperm count or azoospermia, it is important to check their testosterone levels (low levels suggest a production impairment) and LH/FSH. It is also important to screen for the cystic fibrosis (CF) mutation as a congenital bilateral absence of the vas deferens (CBAVD) is a minor variant of cystic fibrosis. Karyotyping is also offered as there may be Y chromosome deletion defects.
52. Surgical Sperm Retrieval Where the sperm quality is low but sperm are present, ICSI is required to help achieve a pregnancy. However, in the absence of naturally ejaculated sperm, patients will have to undergo surgical sperm retrieval (SSR). SSR can be performed under sedation or general anesthetic. A fine needle is inserted into the epididymis or the testicular tissue to obtain sperm or testicular tissue with sperm, respectively. The retrieved sperm can then be cryopreserved or injected into the oocyte as part of a fresh IVF/ICSI cycle.
53. Cryopreservation of gametes Sperm or oocyte can be cryopreserved for later use. Often this process is very useful in preserving fertility for patients undergoing chemo/radiation therapy for cancer. Currently, the pregnancy rate for thawed sperm/egg in top fertility centers is very near to that of normal IVF cycles. This process can also be used for storage of gametes from donors who wish to donate their sperm or eggs for altruistic reasons to help couples with fertility problems.