Subfertility PDF

Dr Alaa yousif mahmood obstetric and gynecology department MRCOG (LONDON)/DOG/M.B.ch.B  objective Theoretical skills Ø Understand epidemiology, aetiology and pathogenesis of infertility. Ø Understand clinical management and prognosis of all aspects of female fertility problem...

Dr Alaa yousif mahmood obstetric and gynecology department MRCOG (LONDON)/DOG/M.B.ch.B  objective Theoretical skills Ø Understand epidemiology, aetiology and pathogenesis of infertility. Ø Understand clinical management and prognosis of all aspects of female fertility problems. Ø Have adequate knowledge of interpretation of relevant investigations in relation to female infertility. Ø Have adequate knowledge of indications and limitations of treatments for female infertility.  Clinical senario Mrs Ahlam is referred to the Gynaecology outpatients because she has been trying to conceive for two years without success. She is a 31-year-old customer service manager; she has been married for five years and neither she nor her husband has any children from previous marriages. Her husband is 35-years-old and is self-employed, working from home most of the time. I. Define infertility, and differentiate between primary and secondary. II. Outline the main aetiological groups for female infertility  Clinical senario You take further history, and Mrs Ahlam tells you that her periods have been irregular since menarche, with cycles as long as four months. The duration of her periods is 3-7 days; occasionally they are heavy, but there is no significant pain. Until she started trying to conceive, she was regulating her periods successfully by using the COCP. Her past medical history includes an appendicectomy aged 9. You examine Mrs Ahlam and find her BMI at 40; she also appears to have a moderate amount of facial hairBased on the above, 1- what is the likely reason Mrs Ahlam has not conceived? 2-Suggest investigations that could confirm your suspicion of Mrs Ahlam underlying disorder. 3-Given that Mrs Ahlamis presenting with infertility, what other investigations would you request and why?  Clinical senario 4- Describe the findings of a normal semen analysis, based on WHO normal values 5- What information obtainable through history would be helpful if you suspected tubal factor infertility to be the underlying cause? 6- Mrs Ahlam investigations reveal an anovulatory disorder. How would you induce ovulation? 7- Which drug would you use and why- what dosage regime would you use? 8- Describe the side effects of ovulation induction.. 9- If Mrs Ahlam was to get pregnant what implications would her BMI have on her pregnancy and labour?  fi nifotttea subfertility sustertility I'mitn Entwining intercourse Infertility inabilitythe 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 couple subfertility may be primary in couples that have never conceived together, or secondary in couples that have previously conceived together  Natural conception A healthy couple having frequent intercourse have about an 18–20% chance of conceiving in a single menstrual cycle.. There is of course a cumulative increase in pregnancy rates over time as couples try for conception. Within 6 months 70% of couples will have conceived, after 12 months 80% and after 24 months 90% of couples will achieve a pregnancy. Both frequency and timing of sexual intercourse impact strongly on the chance of conceiving naturally. Couples having intercourse three times a week are three times more likely to conceive than couples having intercourse once a week.. fervency Chance. of conception  Increased frequency of intercourse should be encouraged in the ovulatory period ovulatorenod Eggs are thought to be fertilizable for about 12–24 hours post ovulation,an in ovulation 24hr post while sperm can survive in the female reproductive tract for up to 72 hours. hrs sperm survive day 172 3 Ovulation usually occurs about 14 days prior to menstruation, with the luteal phase being relatively stable at this length.  factors adversely affect the natural conception rate Ø Age: natural conception declines significantly in the female after 35 years of age. This is due to the decline in oocyte quality and numbers. Ø Smoking: reduces fertility in females and semen quality in males. Ø Coital frequency: stress and anxiety may affect libido and coital frequency and thusi impact on fertility. Ø Alcohol: excessive alcohol is harmful to the fetus, and can also affect sperm quality. Ø Body weight: Over or under weight can affect ovulation; women with a body mass index (BMI) of >29 or 5 cm). Ø Subserosal fibroids have very little impact if present in isolation. Ø Endometrial polyps can reduce the chance of implantation, although this tends not to be absolute. Ø Endometrial scarring (Asherman’s syndrome) from surgery or infection can be associated with lighter periods and a significantly reduced chance of conception.  Male factor 00 Sperm number or quality is an important contributor to subfertility. There is some evidence that sperm counts are falling, and there are various theories that try to explain this, including Ø environmental and dietary issues. dentil orchitisepidy Ø Spermatogonial cells that produce the sperm can be damaged by inflammation (orchitis) or the epididymis that stores mature sperm can also be damaged. Ø Certain iatrogenic influences such as pelvic radiotherapy Ø or surgery for undescended or torted testes can reduce sperm production or damage or block the male reproductive tract. Ø Medical conditions such as diabetes Ø and certain occupations involving contact with chemicals or radiation are associated with male factor subfertility. Ø Occasionally, sperm production may be normal but there are erectile difficulties or problems with ejaculation. Ø Genetic causes of male factor infertility include aneuploidy of sex chromosomes (Klinefelter XXY most commonly) or structural abnormalities of the autosomes, such as inversions, deletions or balanced translocations. Microdeletions of the azoospermic factor \ (AZF) regions of the Y chromosome are associated with low sperm counts and motility  Female investigations Blood hormone profile. early follicular phase follicular-stimulating hormone (FSH), oestradiol and luteinizing hormone (LH). Anti-Müllerian hormone (AMH) is proving particularly helpful in the assessment of ovarian reserve and is independent of the menstrual cycle,.A midluteal progesterone. In women with an irregular menstrual cycle, thyroid function, prolactin and testosterone. Chlamydia testing should be offered prior to any uterine instrumentation. If ART is to be offered, viral screening for human immunodeficiency virus (HIV) and hepatitis B and C should be offered. Transvaginal ultrasound (TVUSS) should be performed where possible. This provides an accurate assessment of pelvic anatomy Tubal potency testing may be necessary  Test for ovulation Ovulation can be detected by several methods ovulation predictor test, onulation predicar test basal body temperature (BBT) chart, Gaval body temp ultrasound, blood progesterone level, and endometrial biopsy. The first two methods are most commonly used.  Ovulation Predictor Test: This test detects the surge of the hormone LH (luteinizing Hormone) in the urine or the rise of the hormone estrogen in saliva. The urinary test is more commonly used and more reliable of the two methods. 24 48hr Approximately 24-48 hours prior to ovulation, the hormone LH rises and falls over a 24-hour period. This is a signal for the egg to undergo final maturation, and also a means to predict when ovulation will occur (hence the name predictor test). Conception by natural means (intercourse) or artificial means (insemination) should be timed by the LH surge detector to the day of or the day after the LH test becomes positive.  Basal Body Temperature (BBT) Chart : After ovulation, body temperature in normally ovulating women increases by one half to one degree Fahrenheit for two weeks. If pregnancy does not occur, the temperature drops to baseline at the time of menses. The basal body temperature remains elevated if pregnancy occurs. Measuring BBT allows one to retrospectively confirm ovulation. Intercourse or insemination should occur right before the temperature rise. The temperature must be taken immediately upon awakening, before any body movement, after at least two hours of sleep.  Ultrasound follicle growth monitoring by ultrasound and after ovulation, the fluid-filled cavity (follicular cyst), which contained the egg, collapses. This collapse is a presumed evidence of ovulation  Progesterone Level After ovulation, the hormone progesterone rises gradually until it reaches a peak 7-10 days later. High progesterone level, when performed 7-10 days after ovulation, confirms that ovulation has occurred and that progesterone production for that cycle is normal. Low progesterone level indicates either that ovulation has not occurred or that there is inadequate progesterone production (luteal phase deficiency).  Endometrial Biopsy The lining of the uterus changes predictably after ovulation. Testing a small sample of the lining (endometrial biopsy) may determine whether ovulation has occurred and whether progesterone production is adequate. The test involves sampling c the interior of the uterus, normally with a thin plastic suction tube, 7-10 days after ovulation. Because the test is painful and expensive, and because a single blood level of progesterone may provide similar information, biopsies are infrequently performed for studying ovulation.  Tubal patency Tubal patency and an assessment of the uterine cavity are traditionally investigated by hysterosalpingography (HSG) using X-ray, hysterocontrast synography (HyCoSy) using ultrasound or, more recently, 3D hysterocontrast synography There is some evidence that patients deemed at high risk of pelvic pathology could benefit from a more invasive laparoscopy with dye test and hysteroscopy as a dual diagnostic and potentially therapeutic procedure. It is crucial to remember that tubal patency is not equivalent to tubal function. Currently, there is as yet no effective test to check for tubal function. Laproscopy and dye test HSG hycosy  Male investigations semen fluid analysis (SFA). recommend between a 2- and 4-day abstinence from ejaculation before providing the semen sample... If the initial SFA is abnormal it should be repeated 3 months later, to allow adequate time for spermatogenesis, because occasionally an abnormal SFA will result from insults such as viral infections.  WHO normal seminal fluid analysis Parameter Lower reference limit  mangment The management of the couple’s subfertility should be evidence based and relies on an accurate diagnostic evaluation of the history, clinical examination and investigations. Management may be expectant, medical, surgical or a combination of these. Fertility treatment should be individualized to optimize the treatment result  anovulatory infertility This divides the causes of anovulatory infertility into three main categories – ovulatory dysfunction, 1-hypogonadotrophic hypogonadism 2-hypergonadotrophic hypogonadism, E 3-normogonadotrophic anovulation is usually seen in polycystic ovary syndrome.  PCOS of PC05 is Significant abnormalities in the very earliest stages of folliculogenesis may be the root cause of anovulation in PCOS.  Ovulation induction For patients with PCOS ovulatory problems, ovulation induction (OI) is usually the first line of management so long as there is tubal patency and normal semen analysis. anti estrogen The most common ovulation induction agent used is the anti oestrogen clomiphene citrate. Clomiphene binds to oestrogen receptors in the hypothalamus and pituitary. This blocks the normal feedback loops of oestrogen and results in a surge of gonadotrophin release, stimulating the ovary to recruit more follicles for maturation. Approximately 70% of women on clomiphene will ovulate and approximately one-half of these will be pregnant within 6 months of trying. There is a risk of multiple pregnancies (12%) and therefore women on clomiphene should be monitored by ultrasound scans to track the growth of their follicles, identify the time of ovulation and reduce the risk of multiple pregnancy. Jennette In clomiphene-resistant women, alternative strategies include augmentation with metformin, use of aromatase inhibitors and injectable gonadotrophins. Or can also be induced by laparoscopic ovarian drilling (LOD) in PCOS. However, as LOD is a surgical procedure with the attached risks associated with surgery and anaesthesia, it is only appropriate to offer such treatment to women who have not responded to clomiphene treatment. Ø in women with anovulation of hypothalamic origin, OI using injectable gonadotrophins is more effective. gonadotropins  Hypogonadotrophic hypogonadism Failure of the pituitary gland to produce gonadotrophins will lead to lack of ovarian stimulation. There are a number of disorders of the anterior pituitary gland that lead to failure of production of FSH. These include destruction of the anterior pituitary by a tumour (e.g. a benign non- functioning adenoma or craniopharyngioma), by a pituitary inflammatory Reaction as in tuberculosis, or following ischaemia as in Sheehan’s syndrome. Rare congenital causes include Laurence–Moon– Biedl, Kallmann’s and Prader–Willi syndromes. The pituitary can also be damaged by cranial irradiation or surgically at the time of hypophysectomy for a pituitary tumour. Ø Hypogonadotrophic hypogonadism will also occur if pulsatile secretion of GnRH is slowed or stopped. This is seen in hypothalamic dysfunction, commonly secondary to excessive exercise, psychological stress or anorexia nervosa.  Hypergonadotrophic hypogonadism This occurs as a result of failure of the ovary to respond to gonadotrophic stimulation by the pituitary gland. The absence of negative feedback (by oestradiol and inhibin B) from a developing follicle results in excessive secretion of the gonadotrophic hormones FSH and LH. Concentrations of these hormones reach menopausal levels. Hypergonadotrophic hypogonadism classically results from premature ovarian failure , resistant ovary syndrome, describes the occurrence of elevated levels of serum gonadotrophins in the presence of a good reserve of follicles. Abnormalities in the FSH receptor may produce this picture.  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, namely poor and hyper-response.  In the human ovary, primordial follicles are present by 20 weeks. By 26 weeks, pre- antral follicles (primary and secondary) are formed. AMH inhibits the transition from the primordial to the primary follicular stage. AMH is also important in the regulation of FSH induced oocyte growth and the cyclic selection of the dominant follicle.  Surgery Surgery to treat subfertility can be helpful in a variety of different scenarios. minimal access surgery (MAS) for Investigation of infertility and tubal potency testing by is undertaken if the patient is symptomatic or if specific therapeutic treatment is planned. There is good evidence that laparoscopic ablation of endometriosis can help improve natural conception rates. Often surgery may be used as an adjunct to ART. For example, the surgical disconnection of the tubes from the uterus or removal of hydrosalpinges is associated with a significant improvement in in-vitro fertilization (IVF) success rates Some Submucosal fibroids, endometrial polyps, Asherman syndrome and some congenital uterine anomalies, such as a septum, are usually managed hysteroscopically.. Photograph of a right hydrosalpinx.  Unexplained infertility Completion of standard investigation of infertility fails to reveal a cause in 15–30 per cent of cases. This does not indicate absence of a cause, but rather the inability to identify it. The results of IVF have shown that there may be undiagnosed problems of oocyte or embryo quality or of implantation failure, neither of which can easily be tested unless IVF is undertaken. Unexplained infertility causes great distress to couples, who often find it harder to bear when a cause cannot be found.