Infertility Rhian Allen & David Rogers http://www.worldofsurrogacy.com
Objectives Definition & Epidemiology Female Gonadal Axis Normal Menstrual Cycle Causes Patient History Patient Examination Investigations Treatments Reference
Definition & Epidemiology Definition Failure to conceive despite regular unprotected sex for at least 1 year 2 Sub-types: Primary infertility - Where a couple who has never successfully conceived in the past has difficulty conceiving Secondary infertility - Where a couple who has been able to conceive at least once, are now unable to do so Epidemiology Affects: ~1/7 couples (16%) ~3.5 Million people in the UK For every 100 couples trying to conceive: 84 will conceive within 1 year 92 will conceive within 2 years 93 will conceive within 3 years
Female Gonadal Axis Pulsed GnRH (Gonadotropinreleasing hormone) released by hypothalamus Frequency of pulse determines if LH or FSH is released by the Anterior Pituitary Gland LH or FSH released depending on stage of menstrual cycle https://geekymedics.com/how-the-gonadal-axis-works/
Normal Menstrual Cycle Reminder Day 1 1st bleed Days 1-14 Follicular phase Day 15-28 Luteal phase FSH: High for 1 st 5 days Stimulates development of 1 follicle Follicle produces oestrogen: Proliferative endometrium & cervical mucus (clear & stringy) Controls FSH & LH levels When level high enough (day 14) LH surge & Ovulation 1 follicle corpus luteum & progesterone Endometrium prepared for implantation https://biology.stackexchange.com/questions/48007/why-do-fshand-lh-hormones-drop-in-diagram-when-maturing-follicle-anddoes-size Fertilisation: Corpus luteum breaks down Progesterone falls Menstruation
Causes of Infertility Anovulation 21% Tubal factors 15-20% Endometriosis 6-8% Male factor 25% Unexplained 28%
Females Causes: Ovulatory problems 30% of female infertility cases, 70% can be treated successfully Hormonal Failure to produce mature egg Polycystic ovarian syndrome (PCOS) Hypothalamic malfunction, Pituitary malfunction Too much/too little LH and FSH Prevents maturation of ovum anovulation Scarred ovaries Surgery for ovarian cysts Infection Premature menopause (premature ovarian failure-pof) Idiopathic Genetic- Turner's, Fragile X Follicular problems "Unruptured follicle syndrome"
Females Causes: Fallopian Tube Dysfunction Affects ~25% of infertile couples, has a 30% success rate with best (usually surgical) treatment Infection Usually STI- viral or bacterial - hydrosalpinx Abdominal disease E.g. appendicitis & colitis Previous surgery Adhesions Ectopic pregnancy Congenital defects https://en.wikipedia.org/wiki/hydrosalpinx
Females Causes: Endometriosis Very common, affects 30-50% of women with normal fertility Adversely affects fertility in 5-10% of women http://www.globalwomenconnected.com/endometriosis/
Females Causes: Other Variables Abnormal uterus 10% of cases Fibroids Very common Can affect fertility only if they are bulging into the uterus Polyps Good clinical evidence to remove them Significant fertility difference between preand post-polypectomy Congenital abnormalities Septate uterus Problems with keeping pregnancy rather than getting pregnant Dysfunctional cervical mucus Wrong volume or consistency https://www.researchgate.net/figure/272513058_fig9_figure-7-magnetic-resonance-image-ofbicorporeal-septate-uterus-class-u3c-showing
Females Causes: Behavioral Diet & Exercise High or low BMI Smoking Decreases chances of conceiving naturally or by IVF by 1/3!!! http://www.bbc.co.uk/news/uk-wales-24460540 http://www.bbc.co.uk/newsbeat/article/34548964/a-doctor-reveals-the-truth-about-the-risks-of-smokingduring-pregnancy
Male Causes Accounts for 40-50% of infertility 7% of males are affected Spermatogenesis Low sperm count (oligozoospermia) 90% of cases Poor Sperm motility (asthenospermia) Abnormal sperm shape (teratospermia)
Male Causes: Risk factors Behavioral Smoking Alcohol Cannabis Anabolic steroids Sexually transmitted diseases (all lower sperm count) Varicocele Aging Medical Testicular Ca/Radiation treatment https://uk.pinterest.com/ftmwarrior/cigars/
Male Causes: Retrograde Ejaculation Surgery to bladder or prostate Diabetes MS Spinal cord injury/surgery Alpha-blockers Anti-depressants/anti-psychotics Aging https://radiologykey.com/sympathetic-plexus-dysfunction/
Male Causes: Structural Abnormalities Cryptorchidism Non-descended testes Hypospadias Blockage (or lack of) tubes that transport sperm - causing low sperm count Vas deferens Ejaculatory ducts Epididymis http://www.mayoclinic.org/diseases-conditions/hypospadias/home/ovc-20252806
Patient History Female Male Full medical history Menstrual history Past pregnancies (Miscarriages??) Contraception methods Pelvic infections Abdominal surgery Drug and alcohol use Full medical history Age of puberty Past fatherhood Venereal infections, adult mumps Abdominal surgery (hernias, orchidopexy) Erectile problems Job (home during ovulation?) Drug and alcohol use
Patient History Female Male Mood Feeling about diagnosis Frequency of intercourse
Patient Examination Female Male General health Sexual development BMI Signs of PCOS General health Sexual development Penile abnormalities Varicoceles BMI (>25: 60% less sperm, 40% more abnormal sperm) Secondary sexual characteristics Gynaecomastia? Testicular volume (normal: 15-35ml) PR (selective examination if symptomatic) may reveal prostatitis
Investigations: Female Chlamydia screen Chlamydia is commonest cause of tubal infertility problems Immune response damages fallopian tubes Screen as tubal patency test can reactivate dormant bacterium Baseline hormonal profile Day 2-5 FSH (<10) & LH Mid-luteal progesterone Day 21/28 day cycle (>30 indicates ovulation) TSH, Prolactin, & Testosterone Rubella status TVS (Transvaginal USS) Rule out adnexal masses, submucosal fibroids or endometrial polyps. Confirm PCOS Tubal patency (14% of fertility problems) Hysterosalpingogram (HSG) Not used as much today, unpleasant! Tubal "fill" and "spill False positives if tubes spasm ABX needed to reduce risk of pelvic infection Laparoscopy with dye Preferred method Blockage: dye doesn't flow into peritoneal cavity HyCoSy Hysterosalpingo-Contrast Sonography
Investigations: Female Hysterosalpingogram Laparoscopy with dye http://www.wagynaescope.com.au/laparoscopy-and-dye-test/ http://www.yelp.com/biz_photos/randy-s-morris-md-naperville-2?select=t9xf3hsxqrhpw3hs1j5ow
Investigations: Female Hysterosalpingo-Contrast Sonography Newer technique Catheter inserted into uterus & balloon inflated. Dye injected and flow monitored by USS http://www.ultrasoundcare.com.au/services/pelvic-ultrasound-guided-procedures-hy-co-sy.html
Investigations: Male Semen analysis Volume 1.5ml (mean 2.75ml, in 1940s was 3.4ml) Count Highest in Spring and lowest in Summer Normal 15 million sperm/ml (mean 66 million/ml, in 1940s was 113 million/ml, average is falling!) Morphology 40% motile within 1hr of ejaculation 4% normal form Infection? Selective test Culture Two samples taken 3/12 apart Spermatozoa cycle length (64 days) If first sample is normal then no need to take a second http://www.cbsnews.com/pictures/sperm-15-crazy-things-you-should-know/2/
Investigations: Male Bloods Plasma FSH Selective test Primary or Secondary testicular failure Testosterone and LH Androgen deficiency Agglutination tests Abs to sperm http://www.ehow.co.uk/how_6169392_treat-antisperm-antibodies.html
Treatment: Female Ovulatory Anovulation Class I (hypothalamic pituitary failure) menstrual cycle BMI Athletes Px: Pulsed gonadotrophin releasing hormone Anovulation Class II (hypothalamic pituitary dysfunction) Largest group here are PCOS patients Px: Clomiphene 50-100ml/24h on days 2-6 of cycle Anovulation Class III (Ovarian failure) 1 st line Px: Clomiphene/FSH injections (IM) IVF using donated ova PCOS In vitro fertilisation (IVF) Tubular Surgery may help Tubal catheterisation Hysteroscopic cannulation IVF Endometriosis Severe form with abdominal adhesions Laparoscopy to free adhesions and remove areas of endometriosis Numerous treatment options depending on the cause
Treatment: Male Address lifestyle factors (alcohol, smoking, Se, Zn, vitamin C) Azoospermia Use donor sperm Sperm autoimmunity Intra-cytoplasmic sperm injection (ICSI) Sperm injected without tail Check for cystic fibrosis (CF) carrier status if azoospermic or oligpspermic (more likely in these cases) Severe oligospermia CF Erectile dysfunction Artificial insemination https///www.flickr.com/photos/tahefertilidad/5453265785 Intra-cytoplasmic sperm injection is the usual treatment of choice
Treatment: Male Male genitourinary tract infection ABX Treating infection doesn't usually restore fertility Retrograde ejaculation ICSI Varicocele Controversial as 15% males have this with normal fertility ICSI http://www.sunflowerhospital.in/scrotal-sonography.php
Treatment: Both Sexes Hyperprolactinemia Remove cause (if possible) E.g. pituitary microadenoma Bromocriptine 2mg/24h PO Behavioral Lifestyle changes Stop Smoking Reduce BMI https://www.pinterest.com/pin/394135404863242588/
References Picture references shown in slides in red. Accessed on 25/5/17 Collier, J, Longmore M, Amarakone K, editors. Oxford handbook of clinical specialities. 9th ed. Oxford: Oxford University Press; 2013. https://web.stanford.edu/class/siw198q/websites/reprotech/new%2 0Ways%20of%20Making%20Babies/Causefem.htm http://umm.edu/health/medical/reports/articles/infertility-in-men