Infertility Thomas Lloyd and Samera Dean
Infertility Definition Causes Referral criteria Assisted reproductive techniques Complications Ethics
What is infertility? Woman Reproductive age Has not conceived after 1 year of unprotected intercourse Regular and at least twice a week Investigate both the woman and partner
Primary and Secondary Infertility Primary = no previous pregnancy Secondary = previously succeeded in achieving at least one pregnancy termination, miscarriage and ectopic
NICE Guidelines https://www.nice.org.uk/guidance/cg156/cha pter/introduction Affects 1 in 7 heterosexual couples On average a GP can expect to see approximately 2 infertile couples each year Role of the GP - correct advice, investigations, management and referral Range of causes so investigation is crucial
Male disorders (30%) Unexplained (25%) Main Causes Ovulatory disorders (25%) Tubal damage (20%) Uterine or peritoneal disorders (10%) Multiple factors (15%) 40% of causes found both in the man and woman
Initial Assessment Menstrual history Medical history - hypo/hyperthyroidism, prolactinoma, PCOS, hypothalamic pituitary disease, anorexia, weight loss, Cushing s disease, PID, STDs Abdominal operations Smoking, alcohol, drugs Coital and social history
Examination General examination Pelvic examination? (hysterosalpingogram) Female BP Female BMI
Investigations I No conception -> after 2 years of regular unprotected intercourse. 1Semen analysis. 2Day 2-5 FSH (Follicle Stimulating Hormone) and LH (Leutinizing Hormone). Where available, AMH (anti-mu llarian hormone) 3Mid-luteal progesterone. 4HSG (Hysterosalpingography)
Investigations 2. 1 Serum prolactin. 2 Thyroid function tests. 3 Serum testosterone. 4 SHBG (sex hormone binding globulin). 5 Oestradiol.
6 DHEAS. 717aOH Progesterone Investigations 3. 8USS (ultrasound scan) 9FBC, U&E, ESR and random blood sugar 10Karyotype. Turners syndrome (45XO), Triple X (48XXX) 11Ref: http://www.infertilitynetworkuk.com/uploaded/fact%20sheets/gp%20info%20fertility%20tr eatment.pdf
Unexplained infertility Offer IVF treatment Women who have not conceived after 2 years of regular unprotected intercourse NHS access varies across the UK (HFEA - funding) Do not offer oral ovarian stimulation agents - subject of debate! Clomifene citrate, anastrozole or letrozole
Referral criteria Offer referral for specialist opinion when Woman 36+ Known hx of infertility or predisposing factors Unexplained infertility DO NOT offer ovarian stimulation to women with unexplained infertility Offer IVF-to women with unexplained infertility who have not conceived after 2 yrs
Referral criteria II A full IVF cycle +/- intracytoplasmic sperm injection (ICSI), should comprise one episode ovarian stimulation and transfer of resultant fresh and frozen embryos In under 40, who after 2 yrs of regular sex haven t conceived or 12 cycles of artificial insemination (where 6+ are by intrauterine insemination) offer 3 cycles of IVF +/- ICSI. If reaches age of 40 during Rx, complete Rx but do not offer any more cycles.
IVF Referral criteria III In 40-42yo who have not conceived after 2 yrs of regular sex or 12 cycles of artificial insemination (where 6+ are by intrauterine insemination) offer 1 full cycle IVF +/- ICSI, providing 3 criteria fulfilled: Never previously had IVF No evidence of low ovarian reserve There has been discussion of additional implications of IVF and pregnancy at this age.
IVF Referral criteria IV Where no chance of pregnancy, where IVF only management- refer If under 40 with any previous full IVF cycle, self or NHS funded- should count towards total 3 full cycles offered by NHS. Take into account outcome of previous IVF Rx when assessing further IVF Rx
Regulation Human fertilisation and embryolgy authority HFEA (http://www.hfea.gov.uk/) Act under HFE Acts 1990 and 2008 to: Licence and monitor IVF clinics Licence and monitor human embryo research Register licences held by clinics, research establishments, storage centres Regulate gamete stroage Licence IUI, GIFT and other services.
Medical Rx for infertility Clomifene Pituitary gland -> release gonadotrophin hormones -> stimulate ovulation Metformin PCOS Not responded to clomifene
Surgical Rx for infertility For male In obstructive azoospermia- correct empididymal blockage -as alternative to IVF/ surgical sperm recovery. Varicocele surgery not offered as no improvement. For female In mild tubal disease- surgery Proximal tubal obstruction- surgery. Hydrosalpinges- salpingectomy by laparoscopy before IVF If amenorrhoea due to adhesions- surgery. Ablate endometriosis (all severities) Ovarian drilling in PCOS
Assisted reproduction techniques What? How? When to use it? In Vitro Fertilisation (IVF) Intra-cytoplasmic sperm injection (ICSI) Intrauterine insemination (IUI) Gamete intra-fallopian transfer (GIFT)
Intrauterine insemination (IUI) How Washed suspension of sperm (various methods)- to separate non motile/ motile sperm. More motile sperm placed in womb near ovulation. Can use medications to induce superovulation (clomifene)- Not NICE recommended. When Unexplained infertility Male partner has impotence/ premature or retrograde ejaculation, low sperm count, low mobility Making baby with donated sperm.
How In Vitro Fertilisation (IVF) - Less invasive than GIFT and can select embryos Suppress monthly cycle (GnRH agonists/antagonists) for ~2 wks FSH to stimulate ovulation Oocyte retrieval US guided Fertilisation of eggs- cultured in lab, grown in incubator Embryo transfer (number restricted -multiple birth risk) Complications- ovarian hyperstimulation, multiple pregnancy When- Unexplained infertility Fallopian tubes blocked IUI/ fertility drugs ineffective
In Vitro Fertilisation (IVF) Risks 1. Drug reaction 2. Ovarian hyperstimulation syndrome Potentially fatal Avoided by careful gonadotropin use and monitoring At risk- PCOS and under 30s OHSS sudden increase in vascular permeability- ascites. Causes loss in intravascular volume, haemoconcentraion, oliguria. Secondary hyperaldosteronism causes salt retention. Peripheral oedema occurs. Can be mild-mod-severe. Death from CV thrombosis, renal failure, cardiac tamponade 3. Multiple pregnancy Increases risks. 30% of twins become singletons in first trimester All obstetric complications increased. Social effects
Intra-cytoplasmic sperm injection (ICSI) How Standard IVF requires 500,000 sperm If lower, can be assisted by micromanipulation techniques. Sperm immobilised before ICSI Injected directly into cytoplasm of oocyte. Fertilisation as good as 60% Pregnancy rates as good as IVF Ethical issues? When- profound oligozoospermia, athenoteratozoospermia, obstructive azoospermia, IVF failure, ejaculation problems
Gamete intra-fallopian transfer (GIFT) How Goes further than IUI/ superovulation Collects oocytes Direct transfer of oocytes and sperm into fallopian tube Disadvantages- requires laparoscopy and has a complicated ovarian stimulation regimen. Doesn t give fertilised oocytes. When Unexplained fertility Fallopian tubes not damaged/ blocked Low sperm count IVF objections/ failure
Ethics IVF- should everyone get a cycle? What about the bypassing natural selection?- ICSI Could parental choice go too far?
References and further reading NICE clinical guidance 156 Assessment and treatment for people with fertility problems, issued February 2013 National Institute of Child Health and Human Development Website http://www.nichd.nih.gov/pages/index.aspx Human Fertilisation and embryology authority website http://www.hfea.gov.uk/index.html Infertility in practice 3 rd Edition. Adam H Balen 2009, ISBN-10 0415 45067 5