Infertility Flashcards
What percent of patients will concieve within a year of regular unprotected sex?
85%
Regular = 2-3 times a week
What proportion of couples will struggle to conceive naturally?
1 in 7
When should investigation and referreal for infertility be initiated?
After the couple has been trying to conceieve without success for 12 months (this can be reduced to 6 months if the woman is older than 35 as her ovarian stores are already reduced and time is more precious)
What are some causes of infertility?
Sperm problems (30%)
Ovulation problems (25%)
Tubal problems (15%)
Uterine problems (10%)
Unexplained (20%)
40% of infertile couples have a mix of male and female causes
What is some general lifestyle advice for couples trying to get pregnant?
Woman should be taking 400mcg of Folic acid daily
Aim for healthy BMI
Avoid smoking and drinking excessive alcohol
Reduce stress as this may negatively affect libido and the relationship
Avoid timing intercourse
What are some initial investigations in primary care for infertility?
BMI (low indicates anovulation, high indicates PCOS)
Chlamydia screening
Semen analysis
Female hormonal testing
Rubella immunity in the mother
What does female hormone testing for infertility involve?
Serum LH and FSH on day 2 to 5 of the cycle
Serum progesterone on day 21 of the cycle (or 7 days before the end of the cycle if not a 28-day cycle).
Anti-Mullerian hormone
Thyroid function tests when symptoms are suggestive
Prolactin (hyperprolactinaemia is a cause of anovulation) when symptoms of galactorrhea or amenorrhoea
What does a high FSH indicate for infertilty?
Poor ovarian reserve (the number of follicles that the woman has left in her ovaries). The pituitary gland is producing extra FSH in an attempt to stimulate follicular development.
What does a high LH suggest for infertility?
Polycystic ovarian syndrome
What does a rise in progesterone on day 21 indicate?
That ovulation has occurred and the corpus luteum has formed secreting progesterone
Why is anti-mullerian hormone measured in infertility?
Most accurate marker of ovarian reserve – released by the granulosa cells in the follicles and falls as the eggs are depleted – high level indicates a good ovarian reserve
What are some further investigations in primary care for infertility?
Ultrasound pelvis to look for polycystic ovaries or any structural abnormalities
Hysterosalpingogram to look at the patency of the fallopian tubes
Laparoscopy and dye test to look at the patency of the fallopian tubes, adhesions and endometriosis
What is a hysterosalpingogram?
Scan used to assess the shape of the uterus and patency of the fallopian tubes – helps with diagnosis and has a therapeutic benefit – increases the rate of conception without any other intervention
What intervention can be performed during a hysterosalpingogram?
Tubal cannulation under x-ray guidance – to open the tubes
How is a hysterosalpingogram performed?
Small tube is inserted into the cervix and a contrast medium injected through the tube – fills uterine cavity and fallopian tubes – x-ray images are then taken
What are the risks of hysterosalpingogram?
Risk of infection with the procedure and often antibiotics are given prophylactically for patients with dilated tubes / history of pelvic infection
What should be screened for before a hysterosalpingogram?
Chlamydia and gonorrhoea
What is involved in a laparoscopy and dye test?
Dye is injected into the uterus and should be seen entering the tubes and spilling out at the ends – during laparoscopy the surgeon can also assess for endometriosis or pelvic adhesions and treat these
What are the management options for anovulation?
Weight loss for overweight patients with PCOS can restore ovulation
Clomifene
Letrozole may be used instead of clomifene to stimulate ovulation (aromatase inhibitor with anti-oestrogen effects)
Gonadotropins may be used to stimulate ovulation in women resistant to clomifene
Ovarian drilling may be used in polycystic ovarian syndrome
Metformin may be used when there is insulin insensitivity and obesity (usually associated with PCOS)
How does clomifene help with anovlation?
It’s an anti-oestrogen given on day 2-6 of the menstrual cycle – stops the negative feedback of oestrogen on the hypothalamus resulting in a greater release of GnRH and subsequently FSH and LH
How can ovarian drilling help with infertility?
Laparoscopic surgery where the surgeon punctures multiple holes in the ovaries using diathermy or laser therapy – improving the womans hormonal profile and resulting in regular ovulation and fertility
How are tubal factors for women with infertility managed?
Tubal cannulation during hysterosalpingogram
Laparoscopy to remove adhesions or endometriosis
In vitro fertilisation (IVF)
How are uterine factors managed in infertility?
Surgery to correct polyps, adhesions or structural abnormalities affecting fertility
What are the management options for sperm problems in infertility?
Surgical sperm retrieval
Surgical correction of an obstruction in the vas
Intra-uterine insemination (ICSI)
Intracytoplasmic sperm injection
Donor insemination
What is surgical sperm retrieval?
When there is a blockage somewhere along the vas deferens preventing sperm from reaching the ejaculated semen a needle and syringe is used to collect sperm from the epididymis through the scrotum
What does intra-uterine insemination involve?
Collecting and separating out high quality sperm then injecting them directly into the uterus of the woman (unclear if this is any better than normal intercourse)
What is intracytoplasmic sperm injection?
Injecting sperm directly into the cytoplasm of an egg – fertilised eggs become embryos and are injected into the uterus of a woman – useful when there are significant motility issues and a very low sperm count along with other issues
What is donor insemination?
Using sperm from a donor is another option for male factor infertility
How can semen analysis help with infertility issues?
Used to examine the quantity and quality of the semen and sperm – assesses for male factor infertility
What instructions are men given on sperm samples?
Abstain from ejaculation for at least 3 days and at most 7 days
Avoid hot baths, sauna and tight underwear for the lead up to providing a sample
Attempt to catch the full sample
Deliver the sample to the lab within 1 hour of ejaculation
Keep the sample warm (e.g. in underwear) before delivery
What factors may affect semen analysis?
Hot baths
Tight underwear
Smoking
Alcohol
Raised BMI
Caffeine
When will a repeat semen sample be needed?
After 3 months in borderline results or 2-4 weeks with very abnormal results
What are normal sperm results according to the WHO?
Semen volume (more than 1.5ml)
Semen pH (greater than 7.2)
Concentration of sperm (more than 15 million per ml)
Total number of sperm (more than 39 million per sample)
Motility of sperm (more than 40% of sperm are mobile)
Vitality of sperm (more than 58% of sperm are active)
Percentage of normal sperm (more than 4%)
What is polyspermia?
High number of sperm in the semen sample (more than 250 million per ml)
What is normospermia?
Refers to normal characteristics of the sperm in the semen sample
What is oligospermia?
Reduced number of sperm in the semen sample, classified as:
Mild oligospermia (10 to 15 million / ml)
Moderate oligospermia (5 to 10 million / ml)
Severe oligospermia (less than 5 million / ml)
What is cryptozoospermia?
Very few sperm in the semen sample (less than 1 million / ml)
What are some causes of reduced sperm quality or quantity?
Hot baths
Tight underwear
Smoking
Alcohol
Raised BMI
Caffeine
What are some pretesticular causes of reduced sperm quality or quantity?
Pathology of the pituitary gland / hypothalamus
Suppression due to stress, chronic conditions or hyperprolactinaemia
Kallman syndrome
Causing hypogonadotrophic hypogonadism (low LH and FSH resulting in low testosterone – necessary for sperm production)
What are some causes of testicular damage causing male infertility?
Mumps
Undescended testes
Trauma
Radiotherapy
Chemotherapy
Cancer
What are some genetic or congenital disorders that result in defective or absent sperm production?
Klinefelter syndrome
Y chromosome deletions
Sertoli cell-only syndrome
Anorchia (absent testes)
What are some obstructive causes of male infertility?
Damage to the testicle or vas deferens from trauma, surgery or cancer
Ejaculatory duct obstruction
Retrograde ejaculation
Scarring from epididymitis, for example, caused by chlamydia
Absence of the vas deferens (may be associated with cystic fibrosis)
Young’s syndrome (obstructive azoospermia, bronchiectasis and rhinosinusitis)
What are the initial steps for investigating abnormal semen analysis?
History
Examination
Repeat sample
Ultrasound of testes
What further investigations may be done on a semen sample?
Hormonal analysis with LH, FSH and testosterone levels
Genetic testing
Further imaging, such as transrectal ultrasound or MRI
Vasography, which involves injecting contrast into the vas deferens and performing xray to assess for obstruction
Testicular biopsy
What is the management of male infertility?
Depends on the underlying cause:
Surgical sperm retrieval where there is obstruction
Surgical correction of an obstruction in the vas deferens
Intra-uterine insemination involves separating high-quality sperm, then injecting them into the uterus
Intracytoplasmic sperm injection (ICSI) involves injecting sperm directly into the cytoplasm of an egg
Donor insemination involves sperm from a donor
How does IVF work?
Fertilising an egg with a sperm in a lab and then injecting the resulting embryo into the uterus – funding criteria are strict and vary between areas – couples are limited to a set number of cycles funded by the NHS
What is the success rate of IVF?
25-30% success rate at producing a live birth
How is intrauterine insemination different from IVF?
More straightforward process and involves injecting sperm directly into the uterus avoiding intercourse – used in cases such as donor sperm for same-sex couples, HIV (avoiding unprotected intercourse) and practical issues with vaginal sex
How does IVF work? Can embryos be used later on?
Cycle of IVF involves a single episode of ovarian stimulation and collection of oocytes (eggs) – single cycle may produce several embryos
Embryos can be transferred separatley in multiple attempts at pregnancy during one “cycle” of IVF - embryos that are not used immediately can be frozen to be used at later date - frozen embryos can potentially be used years later
What are the steos involved in IVF?
Suppressing the natural menstrual cycle
Ovarian stimulation
Oocyte collection
Insemination / intracytoplasmic sperm injection (ICSI)
Embryo culture
Embryo transfer
What are the 2 protocols for suppressing the natural menstrual cycle, preventing ovulation and ensuring the ovaries respond correctly to the gonadotrophins (ie FSH)?
GnRH agonist or GnRH antagonist
How does the GnRH agonist protocol work to suppress the natural menstural cycle?
Injection of GnRH agonist (e.g. goserelin) is given in the luteal phase of the menstural cycle (around 7 days before expected onset of menstrual period) usually day 21 of the cycle
Stilulates the pituitary gland to secrete a large amount of FSH and LH after this initial surge there is negative feedback to the hypothalamus and the natural production of GnRH is suppressed - causing suppression of menstrual cycle
How does the GnRH protocol work to suppress the natural menstrual cycle?
Daily subcutaneous injections of a GnRH antagonist (e.g. cetrorelix) are given starting from day 5-6 of ovarian stimulation - supresses the body releasing LH and causing ovulation to occur
Why is suppression of the natural gonadotrophins (LH and FSH) needed in IVF?
Follicles which are developing would be released before it is possible to collect them
How does ovarian stimulation work in IVF?
Using medications to promote the development of multiple follicles in the ovary - starting at beginning of the menstrual cycle (usually day 2) with subcutaneous injections of FSH over 10 to 14 days - FSH stimulates the development of follicles and this is closely monitored with regular transvaginal ultrasound scans
What is the trigger injection in ovarian stimulation?
When enough follicles have developed to an adequate size (usually around 18 millimetres), the FSH is stopped, and an injection of human chorionic gonadotropin (hCG) is given. This injection of HCG is given 36 hours before collection of the eggs. The hCG works similarly to LH does naturally, and stimulates the final maturation of the follicles, ready for collection. This is referred to as a “trigger injection”.
How are oocytes collected from the ovaries in IVF?
Under guidance of a transvaginal ultrasound scan
Needle is inserted through the vaginal wall into each ovary to aspirate the fluid from each follicle
Fluid contains the mature oocyte from the follicles
Procedure is usually performed under sedation (not general anaesthetic) - fluid from the follicles is examined under the microscope for oocytes
How does oocyte insemination work in IVF?
Male produces a semen sample around the time of oocyte collection - frozen sperm from earlier samples may be used - sperm and egg are mixed in a culture medium - thousands of sperm need to be combined with each oocyte to produce enough enzymes (e.g. hyaluronic acid) for one sperm to penetrate the corona radiata and zona pellucida and fertilise the egg
When is intracytoplasmic sperm injection used?
Male factor infertility
How does intracytoplasmic sperm injection work?
In addition to the IVF process - after the eggs are harvested a semen sample is produced the highest quality sperm are isolated and injected directly into the cytoplasm of the egg
How long does the embryo culture take? What happens?
2 - days left in an incubator to see which grow into a blastocyst stage of development
How does the embryo transfer work in IVF?
After 2-5 days the highest quality embryos are selected for transfer - catheter is inserted under ultrasound guidance through the cervix and into the uterus - a single embryo is injected through the catheter - generally a single embryo is transferred but 2 may be transferred in older women (i.e. over 35 years) any remaining embryos can be frozen for future attempts
When is a pregnancy test performed after egg collection? What could go wrong?
16 days after egg collection - when this is positive implantation has occured
There is the possibility of miscarriage or ectopic pregnancy
What happens if a pregnancy test is negative after implantation?
Hormonal treatment is stopped - woman will go on to have a menstrual period - bleeding may be more substantial than usual given the additional hormones used during ovarian stimuation
How is progesterone given after IVF embryo implantation?
From oocyte collection until 8-10 weeks gestation usually in the form of vaginal suppositories in order to mimic the progesterone that would be released by the corpus luteum during a typical pregnancy (after which the placenta takes over the production of progesterone)
In IVF, when is an ultrasound scan performed to confirm a fetal heartbeat?
Around 7 weeks (also to rule out miscarriage or ectopic pregnancy) - if this is healthy then the remainder of the pregnancy can proceed with standard care
What are the main complications of IVF?
Failure
Multiple pregnancy
Ectopic pregnancy
Ovarian hyperstimulation syndrome
What are the risks of the egg collection procedure?
Pain
Bleeding
Pelvic infection
Damage to the bladder or bowel
What is ovarian hyperstimulation syndrome?
Complication of ovarian stimulation during IVF infertility treatment - associated with the use of human chorionic gonadotrophin to mature the follicles during the final steps of ovarian stimulation
What is the pathophysiology behind ovarian hyperstimulation syndrome?
Increase in vascular endothelial growth factor (VEGF) released by the granulosa cells of the follicles - this increases vascular permeability cauing oedema, ascites and hypovolaemia
The use of gonadotrophins (LH and FSH) during ovarian stimulation results in the development of multiple follicles. OHSS is provoked by the “trigger injection” of hCG 36 hours before oocyte collection (this stimulates the release of VEGF from the follicles)
There is also activation of the RAAS system - notable finding in patients with OHSS is a raised renin level which correlates with the severity of the condition
What are the risk factors for OHSS?
Younger age
Lower BMI
Raised anti-Müllerian hormone
Higher antral follicle count
Polycystic ovarian syndrome
Raised oestrogen levels during ovarian stimulation
How is OHSS risk monitored?
During stimulation with gonadotrophinc they are monitored with:
Serum oestrogen levels (higher levels indicate a higher risk)
Ultrasound monitor of the follicles (higher number and larger size indicate a higher risk)
What strategies can be used to reduce the risk of OHSS?
Use of the GnRH antagonist protocol (rather than the GnRH agonist protocol)
Lower doses of gonadotrophins
Lower dose of the hCG injection
Alternatives to the hCG injection (i.e. a GnRH agonist or LH)
When does OHSS present?
Within 7 days of the hCG injection (early OHSS)
Later than 10 days (late OHSS)
What are the features of OHSS?
Abdominal pain and bloating
Nausea and vomiting
Diarrhoea
Hypotension
Hypovolaemia
Ascites
Pleural effusions
Renal failure
Peritonitis from rupturing follicles releasing blood
Prothrombotic state (risk of DVT and PE)
What are the symptoms of mild OHSS?
Abdominal pain and bloating
What are the symptoms of moderate OHSS?
Nausea and vomiting with ascites seen on ultrasound
What are the features of severe OHSS?
Ascites, low urine output (oliguria), low serum albumin, high potassium and raised haematocrit (>45%)
What are the features of critical OHSS?
Tense ascites, no urine output (anuria), thromboembolism and acute respiratory distress syndrome (ARDS)
What is the management of OHSS?
Supportive with treatment of any complications, involving:
How is OHSS managed?
Oral fluids
Monitoring of urine output
Low molecular weight heparin (to prevent thromboembolism)
Ascitic fluid removal (paracentesis) if required
IV colloids (e.g. human albumin solution)
Where are patients with OHSS managed?
Patients with mild to moderate OHSS are often managed as an outpatient. Severe cases require admission, and critical cases may require admission to the intensive care unit (ICU).
How to assess dehydration in OHSS?
Raised haematocrit can indicate dehydration - this is the concentration of RBCs in the blood
If its raised this indicated less fluid in the intravascular space as the blood is becomming more concentrated
