Infertility & assisted conception Flashcards
How common is infertility ?
Very, affects 1:6 couples (15%)
List some of the reasons for increasing rates of infertility
- Women are older when trying to concieve
- Rise in chlamydia infections
- Increase obesity
- Increase in male factor infertility
- Increased awareness of infertility treatments available
List the factors which increase the chances of conception
- Women < 30
- Previous pregnancy
- < 3yrs trying to concieve
- Intercourse occuring around ovulation
- Womans BMI 18.5-30
- Both partners non-smokers
- Caffeine intake < 2 cups daily
- No recreational drug use
What happens to fertility as we get older ?
Define infertility
This is failure to achieve clinical pregnancy after ≥ 12 months of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child
This can be further divided into:
- Primary = couple have never concieved
- Secondary = couple previously concieved but pregnancy was not successful e.g. misscariage or ectopic pregnancy
What reasurance should be be given to couples presenting with concerns over infertility ?
Reasure that 84% of couples will concieve within the 1st year of having unprotected sexual intercourse & 92% will within 2 years
What is the initial general advice provided to couples wishing/struggling to concieve ?
- Folic acid 400 micrograms (5mg if them or partner have a NTD, or previous baby with NTD, or a fam history of NTD’s or they have diabetes)
- Aim for BMI 20-25
- Advice regular sexual intercourse every 2-3 days
- Smoking, alcohol & caffeine advice
- Stop recreational drugs or methadone
List the general different causes of infertility
- Male factor infertility
- Multiple factors (female & male)
- Multiple factors (female only)
- Tubal factor
- Endometriosis
- Diminished ovarian reserve
- Ovulatory dysfunction
- Uterine factor - structural
- Unexplained
- Other causes
Ovulatory dysfunction is covered in ovulatory disorders deck in Endocrine week 5
What are the causes of tubal disease resulting in infertility ?
- PID - usually due to chlamydia or gonorrhoea resulting in hydrosalpinx or pyosalpinx
- Endometriosis
- Transperitoneal spread from abdo infections e.g. appendicitis, abdominal abscess etc
- Following procedures - IUCD insertion, hysteroscopy, HSG, ectopic pregnancy, sterilisation
- Fibroids
- Polyps
What are the uterine/ structural abnormalities (affecting meeting of egg & sperm) which can result in infertility ?
- Fibroids
- Vaginal septum
- Adhesions
- Polyps
What are the causes of male factor infertility ?
IDIOPATHIC: most common cause (>50%)
OBSTRUCTIVE: vasectomy, cystic fibrosis (congenital absence of vas deferens), infection
NON-OBSTRUCTIVE:
- Congenital: Cryoptorchidism
- Infection: mumps orchitis
- Iatrogenic: chemotherapy/radiotherapy
- Pathological: testicular tumour
- Genetic: chromosomal (Klinefelter’s syndrome, microdeletions of Y chromosome, Robertsonian translocation)
- Specific semen abnormality e.g. globozoospermia
- Systemic disorder
- Endocrine
When should someone be investigated for a cause of infertility ?
Once they meet the definition of it i.e. after 12 months of trying
How should infertility be initially investigated ?
See as couple in designated infertility clinic & carry out:
History: infertility history, gynaecology, andrology, sexual history, social history, PMH, PSH, POH
Examination of female:
- BMI
- General examination, assessing body hair distribution, galactorrhoea
- Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility
Examination of male:
- BMI
- General examination
- Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles
What are the initial female investigations which should be done in someone presenting with infertility ?
- Endocervical swab for chlamydia
- Cervical smear if due
- Blood for rubella immunity
- Midluteal progesterone level (day 21 of 28 day cycle or 7 days prior to expected period in prolonged cycles), progesterone > 30nmol/l suggestive ovulation
- Test of tubal patency: hysterosalpingiogram or laparoscopy
Others if indicated: e.g. hysteroscopy, ultrasound scan, endocrine profile and chromosomes
What is the 1st line investigation for investigating tubal patency ?
1st line = Hysterosalpingiogram (HSG)
Done in women who are not known to have comorbidities/risk factors of tubal/ pelvic pathology e.g. PID, previous ectopic pregnancy or endometriosis) or when laparoscopy is contraindicated i.e. obesity, previous pelvic surgery, Crohn’s disease
What is the 2nd line investigation done for assessing tubal patency and when is it done ?
2nd line = Laparoscopy
Done if:
- They have possible tubal/pelvic disease: e.g.PID
- Known previous pathology: e.g. ectopic pregnancy, ruptured appendix, endometriosis
- History suggestive of pathology: e.g. dysmenorrhoea, dysparunia
- Previously abnormal HSG
When is hysteroscopy performed in the assessment of a women presenting with infertility ?
Only performed in cases where suspected or known endometrial pathology: i.e. uterine septum, adhesions, polyp
When is pelvic ultrasound performed in the assessment of a women with infertility
- Perform when abnormality on pelvic examination: e.g. enlarged uterus /adnexal mass
- When required from other investigations: e.g. possible polyp seen at HSG
If a women being investigated for infertility has an anovulatory cycle or infrequent periods what additional investigations should be done ?
Endocrine profile:
- Urine HCG
- Prolactin
- TSH
- Testosterone and SHBG
- LH, FSH and oestradiol
If a women being investigated for infertility has hirtuism what additional investigations should be done ?
Testosterone and SHBG
If a women being investigated for infertility presents with amenorrhoea what additional investigations should be done ?
- Endocrine profile (as in anovulatory cycle)
- Chromosome analysis
What is the treatment of ovulatory disorders causing infertility ?
Refer to ovulatory disorders deck in endocrine week 5
What are the 2 main reasons reproductive surgery is used in the management of infertility ?
- Primary surgical treatment for infertility
- Surgery to enhance IVF outcome
What are the main conditions causing infertility which are treated by surgery ?
- Pelvic adhesions
- Grade 1& 2 Endometriosis
- Chocolate cysts in Ovary
- Tubal Block
What is the surgical treatment done for infertility due to mild tubal disease ?
Tubal surgery
What is the surgical treatment done for infertility due to proximal tubal obstruction ?
Either selective salpingography + tubal catherterisation or hysteroscopic tubal cannulation
What is the surgical treatment done for infertility due to hydrosalpinges before IVF and why ?
Laproscopic salpingectomy - this is done because it improves the chances of live birth with IVF treatment
What is the surgical treatment done for inferility because of intrauterine adhesions ?
Hysteroscopic adhesiolysis
What is the surgical treatment of endometriosis causing infertility ?
- Minimal or mild endometriosis tx = surgical ablation or resection of endometriosis + laparoscopic adhesiolysis
- Women with ovarian endometriomas tx = laparoscopic cystectomy
- Women with moderate or severe endometriosis tx = surgery
What is the treatment of fibroids causing infertility ?
Polypectomy or myomectomy
What is the treatment of uterine septum causing infertility?
Metroplasty
What is the treatment of unexplained infertility ?
- 1st line = try to concieve for a total of 2 years
- 2nd line = after trying to concieve natrually treat with IVF
List the different causes for needing assisted conception treatment (ACT)
- Endometriosis
- Male factor infertility
- Tubal disease
- Multiple male and female factors
- Unexplained
- Ovulatory disorder
- Multiple female factors
- Fertility preservation in cancer patients
- Treatment to avoid transmission of blood born viruses between patients
- Pre-implantation diagnosis of inherited disorders
- Treatment of single parents or same sex couples
- Others: cryopreservation of gametes for social reasons, treatment when absent/abnormal
What needs to be done before ACT begins ?
- Alcohol: females limit to 4 units per week
- Weight: between 19-29 optimal both male and female
- Smoking: advise to stop smoking
- Folic acid: 0.4mg/day preconception-12 weeks gestation (5mg increase risk NTD/obese)
- Rubella: check if female immune to rubella, if not immunise
- Cervical smears: check up to date according to national screening programme
- Occupational factors: exposure to hazards
- Drugs: prescribed, over-the-counter and recreational such as steroids
- Screen for blood born viruses: hep B/C and HIV
- Assess ovarian reserve: antral follicle count or AMH
- Counselling: offer supportive counselling
List the different ACT avaliable
- Donor insemination
- Intra-Uterine Insemination (IUI)
- In Vitro Fertilisation (IVF)
- Intra-Cytoplasmic Sperm Injection (ICSI)
- Fertility Preservation
- Surrogacy
What are the indications for intrauterine insemination (IUI) ACT?
- sexual problems (physical or psychological) or same sex relationships
- discordant BBV
- unexplained infertility
- mild or moderate endometriosis
- mild male factor infertility
- abandoned IVF
Describe what is done in IUI
- Can be in natural/stimulated cycle
- Prepared semen inserted into uterine cavity around time of ovulation
What are the indications for In vitro fertilisation (IVF) ACT ?
- Unexplained infertility (> 2 years durations) (if < 40 give 3 cycles, if 40-42 only 1 cycle)
- Pelvic disease (endometriosis, tubal disease, fibriods)
- Anovulatory infertility (after failed ovulation induction)
- Male factor infertility (if > 1 X 106 motile sperm)
- Failed Intra-uterine insemination (after 6 cycles)
- Others (pre-implantation genetic diagnosis)
List the main steps that make up IVF ACT
- Down regulation
- Ovarian stimulation
- Oocyte collection
- Fertilisation
- Day 5 after fertilisation - day of transfer & cryopreservation
- Embryo transfer
Describe what down regulation is in relation to IVF
- Down-regulation essentially “turns off” the ovaries to better control ovulation and egg maturation during treatment.
- It allows precise timing of oocyte recovery by using HCG trigger
How is down regulation during IVF treatment achieved ?
Using a GnRH agonist or antagonist.
What are the side effects a patient may experience from recieiving down regulation of their ovaries ?
- Hot flushes and mood swings
- Nasal irritation
- Headaches
How is down regulation of the ovaries confirmed in IVF treatment ?
Using a US scan
Describe what happens during the second stage of IVF treatment (ovarian stimulation)
- The goal of this process is to produce as many eggs as possible for collection
- Patient is given injections of Gonadotrophin Hormone containing either synthetic or urinary gonadotrophins (FSH+/- LH) for 8-14 days
- A trigger shot of HCG (mimics the LH surge) is then given to stimulate ovulation 36hrs prior to oocyte collection
Prior to oocyte collection what does the male partner need to do during IVF treatment ?
Provide semen (needs to abstain for 72hrs prior to this) which then needs to be assesed for:
- Volume
- Density - numbers of sperm
- Motility - what proportion are moving
- Progression - how well they move
What are the risks accompanied with oocyte collection ?
- Bleeding
- Pelvic infection
- Failure to obtain oocytes
After oocyte collection what is done ?
- Search through the follicular fluid
- Identify eggs and surrounding mass of cells
- Collect them into cell culture medium
- Incubate at 370C
What is the 4th stage of IVF treatment ?
Ferilisation - artificially (done outside the women by scientists)
Following fertilisation of the oocyte by scientists during IVF treatment when is the fertilised oocyte (embryo) transferred and what is also done ?
- Embryo is transferred on day 5 after fertilisation
- Cryopreservation of the other collected eggs is done I believe
What happens to fertility as we get older ?
How long after embryo transfer should a pregnancy test be done to confirm if IVF treatment has been successful or not ?
16 days
What are the indications for intracytoplasmic sperm injection (ICSI)?
- Severe male factor infertility (< 1x106)
- Previous failed fertilisation with IVF
- Preimplantation genetic diagnosis
When doing ICSI, if the patient has azoospermia what needs to be done for sperm collection ?
Surgical sperm aspiration - Can be extracted from epididymis (if obstructive) or testicular tissue (non-obstructive)
What are the main complications of assisted reproductive treatments ?
- Ovarian hyperstimulation syndrome (OHSS)
- Multiple pregnancies
- Ectopic pregnancies
What are the signs/symptoms of OHSS?
What assisted reproductive treatment is the most likely to result in OHSS?
IVF
What is done to try to prevent OHSS in IVF treatment ?
Prevention:
- Low dose protocols
- Use of antagonist for suppression (referring to GnRH anatagnoist)
What is the treatment of OHSS?
Treatment before embryo transfer:
- Elective freeze
- Single embryo transfer
Treatment after embryo transfer:
- Monitoring with scans and bloods
- Reduce risk thrombosis: Fluids, TED stockings and fragmin
- Analgesia
- Hospital admission if required IV fluids/more intensive monitoring/paracentesis
List some of the additional problems with assissted reproductive treatments
- No eggs retrieved (very uncommon: 0.2%)
- Surgical risks of oocyte retrieval (bleeding, infection)
- Surgical risks of surgical sperm aspiration (haematoma, infection)
- Failed fertilisation (approx. 4%)
- Problems in early pregnancy: increase miscarriage and ectopic pregnancy
- Increase risk in on-going pregnancy (possible increase in prematurity and intra-uterine growth retardation, congenital abnormalities)
- Psychological problems
- Failed treatment
What is the success rates of IVF treatment ?
Approx. 35%
