Infertility.txt

no possibility of conceiving without treatment

if conception has not occurred after a year of regular unprotected intercourse

15%

• primary: female partner has NEVER conceived
• secondary: female partner has previously conceived even if the pregnancy ended in a miscarriage or TOP

• 1. egg produced: anovulation 30%
• 2. adequate sperm released - 'male factor': 25%
• 3. sperm reach egg to fertilise: tubes damaged 25%; sexual prob 5%; cervical (<5%)
• 4. implantation of embryo: incidence unknown but may account for 30% of unexplained subfertility

mainly due to reduced genetic QUALITY of the remaining oocytes, rather than ovulatory problem

• low oestrogen levels exert POSITIVE FEEDBACK to hypothalamus to causes GnRH pulses
• this stimulates anterior pit to produce FSH and LH which cause growth and maturation of follicles of ovary which contain immature oocyte

• oestradiol (E2) so get NEGATIVE FEEDBACK to hypothalamus and so
• less FSH and LH made
• so the maturing follicles COMPETE for the stimulating hormones and usually one is large enough with enough FSH and LH receptors to survive

inhibit B which suppresses FSH

it releases more oestradiol which causes POSITIVE FEEDBACK so more FSH and LH are released and get LH peak to rupture the ripe follicle and release egg (ovulation) onto ovarian surface where fallopian tube picks it up

follicle becomes a corpus luteum

oestrogen and progesterone to maintain a secretory endometrium suitable for embryo implantation

• involutes and hormone levels fall
• get menstruation 14 days after ovulation

HCG made by trophoblast tissue acts on CL to maintain O+P production until fetoplacental unit takes over at 8-10 weeks gestation

• 1. regular cycles of periods means usually they are ovulatory
• 2. vaginal spotting or more discharge
• 3. pelvic pain = mittelschmertz (means middle pain) around time of ovulation

• pre-ovulation: drops 0.2 degrees C
• luteal phase: rises 0.5 degrees C

conception!

from ovulation to subsequent menstruation

• 1. elevated serum progesterone levels in MID-LUTEAL phase. so if you see low progesterone result - can only be interpreted as showing lack of ovulation if was taken 7 days before next period eg in 28day cycle on day21. if irregular cycle, need repeat prog tests until next period starts.
• 2. USS serially monitor follicular growth and after ovulation show the fall in size and haemorrhagic nature of CL
• 3. urine predictor kit indicates if LH surge has taken place - then ovulation should follow
• 4. temperature charts - not recommended

• 1. HYPOTHALAMUS: hypothalamic hypogonadism: anorexia, stress, exercise
• 2. PITUITARY GLAND: hyperprolactinaemia, pituitary damage
• 3. THYROID GLAND: hyper or hyopthyroidism
• 4. ADRENAL GLAND: adrenal hyperplasia
• 5. OVARY: PCOS, POF

PCOS

trans vaginal

• multiple: 12+
• small 2-8mm follicles
• in an enlarged ovary > 10ml

• 20%
• nb - majority have regular cycles

if they put on weight

5%

• need 2 out of 3:
• 1. PCO on ultrasound
• 2. irregular periods >35 days apart
• 3. hirsutism: clinical (acne or hairy) and or biochemical (raised serum testosterone)

genetic

• disordered LH production, high
• peripheral insulin resistance, so compensatory high insulin levels

• 1. increased ovarian androgen production
• 2. increase adrenal androgen production
• 3. reduced hepatic production of SHBG leading to high free androgen levels

• increased intraovarian androgens disrupts folliculogenesis leading to small ovarian follicles
• and irregular or absent ovulation

increased weight can increase insulin and consequently androgen levels

DM2

• acne
• hirsutism
• irregular periods

• related to high LH or insulin levels
• and high BMI

• low: hypothalamic disease
• high: ovarian failure
• normal: PCOS

• FSH
• LH: high in PCOS
• prolactin: exclude prolactinoma
• TSH
• serum testosterone if hirsutism: may be androgen secreting tumour or CAH

• Bloods: FSH LH TSH prolactin testosterone
• USS: transvaginal
• screening: diabetes, abnormal lipids - fasting lipids and glucose

• 1. DM2: in up to 50%
• 2. gestational diabetes in 30% risk reduced by weight loss
• 3. endometrial cancer: more common in women with many years of amenorrhoea due to UNOPPOSED OESTROGEN action

as have NORMAL oestrogen levels

diet exercise to normalise weight: will result in reduction in insulin levels and improve all PCOS symptoms

1. COCP: regulate menstruation and treat hirsutism

at least 3-4 per year

• cyproterone acetate (can be COCP)
• spironolactone
• but conception must be avoided

topical antiandrogen used for facial hirsutism

metformin: reduce insulin levels as it sensitises body to insulin and so reduces androgen levels and hirsutism and promotes ovulation

when GnRH secreting neurones fail to develop]

• 1. oligo/amenorrhoea
• 2. galactorrhoea
• 3. headaches
• 4. bitemporal hemianopia

• 1. DA agonist: bromocriptine or cabergoline - usually restores ovulation
• 2. surgery if 1 fails or neuro symptoms warrant it

• 1. benign adenoma
• 2. pit hyperplasia
• 3. associated with PCOS
• 4. psychotropic drug SE

• 1. pressure from tumours
• 2. infarction following severe PPH (Sheehans syndrome)

• ovary fails so less oestrogen and inhibin made
• so LESS NEGATIVE FEEDBACK so high FSH and LH levels

as no ovarian follicles to respond!

donor eggs

• bone protection
• OCP or HRT

• 1. health advice regarding pregnancy
• 2. risks of multiple pregnancy
• 3. use of folic acid
• 4. weight normalisation may restore ovulation: reduce wt in PCOS; increase in anorexia
• 5. treat specific causes eg thyroid or prolactin problems may restore ovulation

• clomifene
• 6 months use limited

• anti-oestrogen
• blocks oestrogen receptors in hypothalamus and pituitary
• as FSH/LH release is normally inhibited by oestrogen, the effect of clomigene is to increase the release of FSH and LH as it fools the pituitary into believing there is no oestrogen

• begninning- day 2-6
• as it can INITIATE process of follicular maturation which is thereafter self perpetuating for that cycle

by ultrasound to reduce risk of multiple follicle maturation and multiple pregnancy

• metformin
• MOA: oral insulin sensitising drug - aim to restore ovulation

it does not promote multiple ovulation so there is no increase in multiple pregnancies and therefore no need for scan monitoring

• if they want HIRSUTISM treated
• avoid multiple pregnancies

• 1. reduce miscarriage rate
• 2. reduce GDM rate

laparoscopic ovarian diathermy: each ovary is monopolar diathermied at a few points for a few seconds

• at same operation check tubal potency using methylene blue insufflation and treat comorbidities eg endometriosis
• lower multiple pregnancy rate

• recombinant FSH +/- LH daily subcut injection to stimulate follicular growth
• monitor follicular development with USS
• once a follicle is of a size adequate for ovulation eg 17mm then the process can be artificially stimulated by injection of HCG (which is structurally similar to LH) or use recombinant LH

• 1. multiple pregnancy
• 2. ovarian hyperstimulation syndrome
• 3. ovarian and breast carcinoma

• clomifene and gonadotrophins are: as >1 follicle may mature
• metformin no increased risk

increases perinatal complications

• gonadotrophins
• rarely clomifene

• overstimulation of follicles which can get VERY LARGE and PAINFUL
• more common in IVF than standard ovulation induction

• hypovolaemia
• electrolyte disturbance
• ascites
• pulmonary oedema
• thromboembolism
• death

• 1. use lowest effective dose of gonadotrophin
• 2. USS monitoring of follicular growth
• 3. coasting: withdraw gonadotrophins but continue pituitary downregulation
• 4. cancellation of IVF cycle - withold HCG injection

• hospitalisation
• resotre intravascular volume
• electrolyte monitoring and correction
• analgesia
• thromboprophylaxis
• drainage of ascitic fluid to increase comfort and breathing

• testis
• dependent on pituitary LH FSH

LH - testosterone production in Leydig cells

control sertoli cells which are involved in SYNTHESIS AND TRANSPORT of sperm

70 days

testosterone and other steroids

• masturbation
• 2-7 days after the last ejaculation
• sample analysed within 1-2hours of production

• 1. semen analysis repeated after 70 days (as it takes 70 days to make new sperm)
• 2. examine scrotum

• volume > 2ml
• sperm count > 20million/ml
• progressive motility > 50%

no sperm present

< 20 million/ml

<5million/ml

absent or low motility

• 1. idiopathic
• 2. drug exposure
• 3. varicocoele
• 4. antisperm Abs
• 5. infections
• 6. testicular abnormalities
• 7. obstruction to delivery
• 8. hypothalamic problems
• 9. retrograde ejaculation

• alcohol
• smoking
• drugs: sulfasalazine, anabolic steroids
• industrial chemicals: solvents

left

after vasectomy reversal

5%

• poor motility
• clumping together of sperm

• epididymitis
• mumps orchitis

• Klinefelter's XXY
• obstruction: congenital absence of vas

• hypothalamic problems
• Kallmann's syndrome
• hyperprolactinaemia

• 1. drug exposure
• 2. testicles should be below body temperature - wear loose clothing, testicular cooling

give gonadotrophins

IUI: intrauterine insemination

IVF

ICSI: intra cytoplasmic sperm injection is used as part of an IVF cycle

• examine for presence of vas deferens
• Ix: check karyotype (in case XXY), cystic fibrosis, hormone profile
• Rx: surgical sperm retrieval - extracted direct from testis and then used for ICSI-IVF

DI: donar insemination

cervical mucus

• 1. tubal damage
• 2. cervical problems
• 3. sexual problems

• 1. infection
• 2. endometriosis
• 3. surgery/adhesions

PID - STI chlamydia causes adhesions to form within and around the fallopian tubes

PID

12

• 1. insertion of intrauterine contraceptive device
• 2. ruptured appendix

• asymptomatic
• pelvic pain
• vaginal discharge
• abnormal menstruation

laparoscopic adhesiolysis and salpingostomy

laparoscopic surgery to remove endometriotic deposits

as it suppresses ovulation

• 1. antibody production: Ab agglutinate or kill the sperm
• 2. infection in vagina or cervix that prevents adequate mucus production
• 3. cone biopsy for microinvasive cervical carcinoma

IUI

impotence can be psychological or organic

psychosexual counsellor

• 1. laparoscopy and dye test: allow visualisation and assessment of fallopian tubes, then hysteroscopy to assess uterine cavity
• 2. hysterosalpingogram
• 3. HyCoSy: transvaginal USS & an ultrasound opaque liquid

• methylene blue dye is injected through the cervix from the outside
• whether it enters or spills from the tubes can be seen, showing whether tubes are patent

women with no history of pelvic damage or infection

• during the follicular phase of the menstrual cycle prior to ovulation
• 1. in order to avoid the risk of inducing an ectopic pregnancy
• 2. to avoid risk of exposing an early embryo to radiation

• instillation of a radio-opaque dye through a small catheter placed in cervical canal into uterine cavity
• x-ray image obtained shows the uterine cavity, outline of fallopian tubes and presence or absence of dye in abdominal cavity
• when dye is seen to flow freely into the abdominal cavity, tubal potency is confirmed

dye spill appears to be loculated or the tube appears to be in an abnormal position

• uterine adhesions
• submucous fibroids
• filling defects

avoids exposure to x-rays

use of USS to image the uterus and fallopian tubes

at the time of gonadotrophin superovulation, washes sperm are injected directly into the cavity of the uterus

1. tubes must be patent: as oocyte still needs to travel from ovary to sperm

• unexplained subfertility
• cervical problems
• sexual problems
• some male factors

live birth rate is 10% per stimulated cycle

• 1. during the long protocol IVF, the pituitary gonadotrophins are suppressed using 2-3 weeks of GnRH agonist: to prevent endogenous LH surge and premature ovulation before oocyte collection
• 2. multiple follicular development then achieved with 2 weeks of daily subcut gonadotophin injections FSH, LH
• 3. eggs collected under sedation by aspirating follicles transvaginally under US control
• 4. eggs incubated with washed sperm and transferred to a growth medium
• 5. trans cervical replacement of embryos into uterus 2-5 days later

no more than 2 in women < 40years to reduce obstetrics and paediatric complications associated with high order multiples

• frozen for future thawing
• FER: frozen embryo replacement

luteal phase support using progesterone or HCG is given until 4-8 weeks gestation

no

normal ovarian reserve: FSH < 12 so sufficient oocytes collected for fertilisation and transfer

35% per stimulated cycle

ICSI

donar insemination

• 1. ovarian failure
• 2. older age >43 yrs
• 3. genetic disease

• 1. donor, goes through a full stimulated IVF cycle,
• 2. her retrieved eggs are fertilised with sperm of woman's partner
• 3. recipient receives oestrogen and progesterone to prepare her endometrium for transfer of fresh embryos

egg sharing - women who need IVF share eggs

• day 3 embryos are 8 cells
• 1/2 cells removed from embryo and DNA examined using PCR or FISH to look for genetic abnormality
• unaffected embryos replaced 2 days later

• 1. couples who are carriers of single gene defects eg cystic fibrosis
• 2. chromosome translocaitons so high risk child with aneuploidy (chr abn eg downs)
• 3. check sex to avoid replacement of male embryos that ay be affected by haemophilia (not for social reasons in UK)
• 4. over 37yrs needing IVF can have embryos screened and only replace normal embryos to overcome age related decline in IVF success rates

• straight: surrogates own eggs
• host: patients eggs go through IVF then transfer embryo into surrogate

• 1. superovulation: multiple pregnancy and OHSS
• 2. egg collection: intraperitoneal bleed, pelvic infection
• 3. pregnancy: multiple, ectopics