Fertility & infertility

In this unit of gynaecology all of aspects of fertility and associated diseases are described.

1. Fertility & infertility (Unit III) Sr. Susmita HALDER Tutor School of Nursing Asia Heart Foundation

2. Introduction The term 'subfertility' may be preferable to infertility, as many of the bars to conception are relative rather than absolute and in about 30% of cases no cause is found.

3. Introduction People who are concerned about their fertility should be informed that over 80% of couples in the general population will conceive within one year if: the woman is aged under 40 years; and they do not use contraception; and they have regular sexual intercourse (every two to three days). Of those who do not conceive in the first year, about half will do so in the second year (cumulative pregnancy rate over 90%). 

4. Introduction Infertility may be due to problems with one or both partners. Natural female fertility declines with age and increasing maternal age is also associated with increased obstetric risks and risk of miscarriage. This should be noted by women who choose to delay their family.

5. Terminology Fertility is defined as a failure to conceive within one or more years of regular unprotected coitus Primary infertility denotes the patients who have never conceived Secondary infertility indicates previous pregnancy but failure to conceive subsequently Fecundability is defined as the probability Of achieving pregnancy within one menstrual cycle. In a healthy young couple it is 20% Fecundity is the probability of achieving a life worth within a single cycle

6. Incidence 80% of couples achieve conception if they so desire within one year of having regular intercourse with adequate frequency Another 10% will achieve the objective by the end of second year search 10% Raman infidel by the end of second year

7. Factors essential for conception Healthy spermatozoa should be deposited in the vagina or at near the cervix The spermatozoa should undergo changes or capacitation acrosome reaction and aquire motility The spermatozoa should go through the cervix into the uterine cavity and the fallopian tubes There should be ovulation The fallopian tube should be patent and the suicide should be picked up by the scenery at end of the tube The spermatozoa should fertilizer suicide at the ampulla of the tube The embryo should reach the uterine cavity after three to four days of fertilization The endometrium should be receptive by oestrogen progesterone cytokines integrins for implantation and Corpus luteum should function adequately

8. Physiological consideration Due to an ovulation infertility is the prior to puberty after menopause but it should be remembered that the girl may be pregnant even before menarche and pregnancy is possible within few months of menopause conception is not possible during pregnancy as the pituitary gonadal axis is suppressed by human chorionic gonadotropin hence no ovulation and during lactation Infertility is said to be relative despite the fact that the patient is our memory but during lactation ovulation and conception can occur however it is fully elected woman pregnancy is unlikely upto 10 weeks postpartum. (Breastfeeding 5 to 6 times a day and spending 60 minutes in 24 hours)

9. Female infertility

10. Etiology Causes of female infertility Disorders of ovulation They may occur at the level of pituitary or hypothalamus as well as at the level of the ovary. If there is amenorrhoea it should be investigated as such and oligomenorrhoea along similar lines.

11. Classification The World Health Organization (WHO) classifies ovulation disorders into three groups: Group I:  hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism).

12. Classification Group II:  hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovarian syndrome). Group III:  ovarian failure.

13. Classification Women with WHO Group I ovulation disorders: Should be advised that they can improve their chance of regular ovulation, conception and an uncomplicated pregnancy by: Increasing their body weight if their BMI is <19. Moderating their exercise levels if they undertake high levels of exercise.

14. Classification Women with WHO Group II ovulation disorders: Should be advised to lose weight if their BMI is >30, as this alone may restore ovulation, improve their response to ovulation induction agents, and have a positive impact on pregnancy outcomes Those women taking clomifene citrate should have an ultrasound monitoring during at least the first cycle of treatment to ensure that they are taking a dose that minimises the risk of multiple pregnancy.

15. Etiology According to FIGO manual 1990 causes are Tubal & peritoneal factors 25-50 % Ovulatory dysfunctions 30- 40 % Endometriosis 1- 10%

16. Etiology Causes of ovarian failure: Pituitary tumours can displace or destroy normal tissue and the production of follicle-stimulating hormone (FSH) and luteinising hormone (LH) is often the first to be affected. Panhypopituitarism is also called Simmonds' disease.

17. Etiology Sheehan's disease is pituitary infarction following postpartum haemorrhagic shock. Hyperprolactinaemia may present with galactorrhoea or amenorrhoea. The control of prolactin (PRL) is unlike the other releasing factors, in that it is controlled by an inhibiting rather than a releasing factor from the hypothalamus into the hypothalamic-pituitary portal circulation. It is also released in response to thyrotropin-releasing factor, as is thyroid-stimulating hormone (TSH), and so it is elevated if thyroxine is low.

18. Etiology The pituitary gland may be responsible for other disorders such as Cushing's syndrome. A number of chromosomal disorders result in inadequate ovarian function and usually primary amenorrhoea.  

19. Etiology Turner syndrome - There is a loss or abnormality of the second X chromosome in at least one cell line in a phenotypic female. The ovaries are usually just streaks. This condition may be a mosaic. In testicular feminisation there is primary amenorrhoea. The karyotype is XY but there is androgen insensitivity. XXY or Klinefelter's syndrome appears as a male.

20. Etiology The XXX karyotype - this is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. While fertility in women with trisomy X is generally considered normal, there is an increased risk for premature ovarian failure.

21. Etiology Premature ovarian failure or premature menopause (menopause that occurs <40 years, although many gynaecologists use <45 years) causes secondary amenorrhoea. Premature ovarian failure occurs in about 1% of women.

22. Etiology Polycystic ovarian syndrome is usually, but not always, associated with obesity. Sclerocystic ovaries fail to ovulate but they can be very sensitive to clomifene.

23. Etiology Luteal phase defect LPD In this condition there’s inadequate growth and function of corpus luteum↪️ inadequate progesterone secretion ↪️hinders implementation Decreased FSH LH elevated prolactin, subclinical hypothyroidism, older women, dysfunctional uterine bleeding↪️ defective folliculogenesis Luteinised unruptured Follicular syndrome or trapped ovum is associated with pelvic endometriosis or with hyperprolactinemia

24. Etiology Problems of tubes, uterus or cervix The Fallopian tubes are delicate structures whose cilia waft the ovum, or even early embryo, to its destination for implantation - more correctly called nidation.

25. Etiology Damage to the tubes may occur as a result of infection: A history of pelvic inflammatory disease (PID) is highly suggestive of damage to tubes. Severe pelvic infection following illegal abortion is rarely seen in this country but still occurs in places where termination of pregnancy is illegal or difficult to secure. Even a medical or spontaneous abortion can lead to infection of retained products of conception. Postpartum infection can also affect fertility

26. Etiology Sexually transmitted diseases may cause infertility, largely through associated PID: Chlamydia and gonorrhoea are the most important. Infection may be less direct, and spread from appendicitis is possible, even without overt peritonitis.

27. Etiology Female sterilisation operations involve disruption of the tube and results of attempted reversal are poor: Laparoscopic proof of patency of the tubes is not evidence that they function normally.

28. Etiology Infection can also damage the uterus: Adhesions in the uterus and cervix are called Asherman's syndrome.

29. Deformity of the uterus, such as a septum or bicornuate uterus, may be more likely to cause recurrent abortion than failure to conceive: Significant distortion of the uterine cavity by fibroids can prevent implantation and hence fertility, although the impact on fertility remains a subject for debate. Etiology

30. Etiology The cervix may have been shortened and damaged by a cone biopsy. There may be problems of cervical mucus, including hostility to sperm. Endometriosis may cause such inflammation, adhesion and distortion in the pelvis that it causes tubal infertility: Even when it is much less severe than that, it is commonly associated with subfertility. Whether or not minor degrees of endometriosis contribute to subfertility is still debated.

31. Sign & Symptoms History Enquire about frequency of coitus (ideally two to three times a week) and any prolonged or recurrent absences of one of the partners. Ask about potential physical problems such as inadequate penetration or dyspareunia.

32. Sign & Symptoms Medication history A thorough review of all medication is required with a view to both fertility and possible adverse effects on pregnancy, including teratogenicity.   Legal drugs taken for legitimate purposes may also cause problems: Phenothiazines and the older typical antipsychotics as well as metoclopramide increase levels of PRL. Non-steroidal anti-inflammatory drug (NSAID) use is associated with luteinised unruptured follicles. The patient may be taking drugs like immunosuppressants for autoimmune disease or after transplantation.

33. Sign & Symptoms Past medical history Previous treatment for malignancy (chemotherapeutic agents, such as those used in childhood leukaemia) may result in subsequent sterility. Surgery and radiotherapy may be relevant if they involved the pelvic region. Systemic disease may impair fertility, probably by interference with the hypothalamic-pituitary axis: This may include autoimmune disease such as rheumatoid disease or systemic lupus erythematosus (SLE), although the latter - eg, antiphospholipid syndrome - may be associated with recurrent abortion. Chronic kidney injury can impair fertility. Poorly controlled diabetes mellitus should be improved.

34. Sign & Symptoms General health Even in the absence of systemic illness, poor general health will impair fertility. Enquire about general lifestyle including smoking, alcohol and drug use in addition to exercise and dietary intake.

35. Examination Look for signs of hirsutism: Facial hair may be more profuse than normal, although this should be interpreted in the light of racial norms. Acne may also indicate high androgen levels. There may be a hint of male pattern alopecia with slight bitemporal recession. The pubic hairline may extend up towards the umbilicus in a typical male pattern

36. Examination Abdominal examination should be performed and it must precede bimanual pelvic examination or it is very easy to miss a large mass like a big ovarian cyst.

37. Examination Gynaecological examination, especially vaginal examination, may indicate undisclosed sexual difficulties - eg, vaginismus.   Bimanual examination: May find an adnexal mass from an ovary of tubo-ovarian mass or tenderness suggesting PID or endometriosis. Uterine fibroids can distort the uterus and interfere with implantation.

38. Aim for an ideal BMI: Women with a BMI of <19 and who have irregular menstruation or are not menstruating should be advised that increasing body weight is likely to improve their fertility. Women with a BMI of 30 should be informed that they are likely to take longer to conceive and those who are not ovulating should be informed that losing weight is likely to increase their chance of conception. Prevention

39. Participating in a group programme involving exercise and dietary advice, rather than receiving weight loss advice alone, leads to more pregnancies. Smoking cigarettes impairs fertility and smoking in pregnancy increases the risk of miscarriage, obstetric complications, intrauterine growth restriction and even delayed reading ability (at least to the age of 7). Prevention

40. Excessive alcohol consumption impairs fertility. Women who are trying to become pregnant should be informed that drinking no more than 1 or 2 units of alcohol once or twice per week and avoiding episodes of intoxication reduce the risk of harming a developing fetus. There is currently insufficient evidence for a strong association between excessive caffeine consumption and poor pregnancy outcomes, including infertility.  Prevention

41. Illicit drugs should be avoided. Some have adverse effects on fertility or the fetus or both and, for most, the question of teratogenicity has not been adequately addressed. Cannabis can impair ovulation and cocaine can cause tubal infertility. There is also reason to be concerned about the effect these drugs may have in pregnancy. Prevention

42. Assisted conception Assisted conception broadly refers to procedures whereby treated or manipulated sperm are brought into proximity with oocytes Treatment

43. Treatment It includes: Intrauterine insemination (IUI) with partner or donor sperm (in natural or stimulated cycles) Gamete intrafallopian transfer (GIFT) In vitro fertilisation and embryo transfer (IVF-ET) Intracytoplasmic sperm injection (ICSI)

44. Treatment The Human Fertilisation and Embryology Authority (HFEA) has published data showing that there are wide variations in the success rates of IVF clinics. Success depends upon numerous factors, including the woman's age, BMI, previous pregnancy history and lifestyle factors. Around 25% of IVF treatments using a woman's own fresh eggs result in a live birth.

45. Treatment Intrauterine insemination (IUI)  IUI involves the introduction of prepared sperm into the uterine cavity around the time of ovulation (spontaneous or induced). IUI can be considered as a treatment option in the following groups: People who are unable to, or would find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem, who are using partner or donor sperm. People with conditions that require specific consideration in relation to methods of conception (for example, after sperm washing where the man is HIV-positive). People in same-sex relationships. People with unexplained infertility, mild endometriosis or 'mild male factor infertility', who are having regular unprotected sexual intercourse should no longer routinely be offered IUI, either with or without ovarian stimulation. They should be considered for IVF if they have not conceived after trying for two years.

46. Treatment Gamete intrafallopian transfer (GIFT) There is insufficient evidence to recommend the use of GIFT or zygote intrafallopian transfer in preference to IVF in couples with unexplained fertility problems or male factor fertility problems.

47. Treatment In vitro fertilisation and embryo transfer (IVF-ET) When IVF-ET is used: Women aged under 40 years should be offered three cycles. Those women who reach 40 years during treatment should not be offered further cycles. Women aged over 40 years should be offered one cycle of IVF as long as these women: Have never had IVF in the past. Have no evidence of low ovarian reserve. Have had a discussion of the additional implications of IVF and pregnancy at this age. When IVF is used and a top-quality blastocyst is available, a single embryo transfer is now recommended. Currently, double embryo transfer in IVF is the most commonly used strategy in the UK. The new National Institute for Health and Clinical Excellence (NICE) guidelines will change this and, in doing so, will maximise the chance of pregnancy while minimising the risk of a multiple pregnancy.

48. Treatment Intracytoplasmic sperm injection (ICSI) In ICSI, a single sperm is injected directly into an oocyte. It should be considered for those with severe deficits in semen quality, obstructive azoospermia or those with non-obstructive azoospermia. In addition, treatment by ICSI should be considered for couples in whom a previous IVF treatment cycle has resulted in failed or very poor fertilisation. Where the indication for ICSI is a severe deficit of semen quality or non-obstructive azoospermia, the man's karyotype should be established (after genetic counselling).

49. Treatment Ovulation disorder treatment World Health Organization (WHO) Group I ovulation disorder is due to hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism). These women should be advised that they can improve their chance of regular ovulation, conception and an uncomplicated pregnancy by increasing their body weight (for those with a BMI of <19) and/or moderating their exercise levels (if they undertake high levels of exercise). These women should be offered pulsatile administration of gonadotrophin-releasing hormone or gonadotrophins with luteinising hormone activity to induce ovulation.

50. Treatment WHO Group II ovulation disorder is due to hypothalamic-pituitary-ovarian dysfunction (predominately due to polycystic ovarian syndrome). Clomifene citrate (CC) - an anti-oestrogen - is an initial treatment for the majority of these. Metformin (or a combination of clomifene and metformin) can be also considered. However, those women with a BMI of >30 should be advised to lose weight before starting treatment.

51. Treatment Women who are known to be resistant to CC should consider one of the following second-line treatments, depending on clinical circumstances and the woman's preference: Laparoscopic ovarian drilling (by laser or by diathermy) Combined treatment with CC and metformin Gonadotrophins

52. Treatment WHO Group III ovulation disorder is due to ovarian failure - hypothalamic-pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism). Women with ovulatory disorders due to hyperprolactinaemia should be offered treatment with dopamine agonists such as bromocriptine.

53. Treatment General care The couple needs support and reassurance. It can be a very difficult time for them, especially if there is pressure from parents or in-laws, that may be more prominent in some cultures, but can occur in all. Pregnancy probably will occur even without intervention but they must not feel neglected or that nothing can be done. There are many stories of couples who conceive after giving up hope

54. Treatment Couples who have fertility problems should be informed that they might find it helpful to contact a fertility support group. Counselling may be appropriate for some couples, as fertility problems can cause psychological stress

55. Treatment Women intending to become pregnant should be informed that dietary supplementation with folic acid (0.4 mg a day) before conception and up to 12 weeks of gestation, reduces the risk of having a baby with neural tube defects. The dose should be 5 mg a day in those women who have previously had an infant with a neural tube defect or those receiving anti-epileptic medication or who have diabetes.

56. Treatment Ovulation predictor kits should be discouraged. Not only do they appear to be ineffective, but making love should be a spontaneous and amorous act, not dictated by a calendar or a kit.

57. Treatment Where conventional medicine offers no help, patients are often tempted by alternative therapies. However, what little evidence there is suggests that they are of no benefit and that, as they have not been properly tested, they may even be teratogenic.

58. Male infertility

59. Thank you 😊