infertility and ART Flashcards
(36 cards)
define fertility, fertility rate, infertility, and fecundity
Fertility = ability to conceive
Fertility rate = number of births per female
Infertility = failure to conceive pregnancy following 12 months or more of unprotected sex
Fecundity = probability of a live birth from one menstrual cycle. Fecundability is probability of conception in one menstrual cycle
infertility is common and possibly becoming more so - provide evidence (not sperm count for this card)
Globally, around 1 in 6 people have experienced infertility at some point
Global decline in fertility rate, not necessarily due to infertility increase tho, but the main reason is socioeconomic, for smaller family size. Correlation of fewer children with more access to education, and of course children are more expensive now
Possible decline in fertility too tho, with Sun et al. (2019) showing a very slight uptick in male and female infertility from around 2010. However, this could be due an increase in reporting infertility as there are more options to help and less shame
sperm count decline -
explain why this is a concern (including key references)
some research showing a noticeable trend of reducing sperm count since the 1970s. Key paper Carlson et al (1992).
study = 15,000 men without known infertility, published between across 60 studies, and found a significant decline in average sperm count from 113 million/ml in 1940 to 66 million/ml in 1990
Levine, et al (2017) 50% reduction in sperm count over last 40 years
Thought to be due to endocrine disrupting chemicals, lifestyle changes etc…
disagreement that sperm count is declining evidence?
Some scientists - Allan Pacey - are sperm counts declining? Or did we just change our spectacles? 2013 believe our counting method is simply more accurate and therefore better at detecting the lower numbers (older tests tended to overestimate).
Also other studies involved in meta-analysis saying ‘declining sperm count’ = flawed, either small sample of men, only men in attending fertility clinics, publication bias (more likely to be published if saying there is a decline)
give some numbers on ability to conceive based on age
At age 25, monthly fecundity rate is around 0.25, everyone should be able to conceive by 12 months. 30 years = 90% people by 12 months, 35 = ~ 80%,
drops quite a bit more for 40, to only 50% of people conceiving within 12 months, and just over 10% for 45 years old
who is the most common cause of infertility in a couple?
EQUAL! Male = 30%, female = 30%
Combined = 20%, unexplained = 20%
three ‘versions’ of infertility in men?
Oligozoospermia: Low sperm count (1 in 20 males; accounts for around one third of couples have difficulty conceiving)
Asthenozoospermia: Low sperm mobility (motility): Sperm movement is impeded meaning they can’t reach the egg
Teratozoospermia: Abnormal sperm. The sperm may have an unusual shape, making it harder to move and fertilize an egg
male infertility can be caused by three main problem areas, sperm production, sperm transport or sexual dysfunction.
what can be the problem in sperm production?
varicoceles - this is a big one, 40% of cases of male primary infertility
Undescended testes (1-9% of full-term male infants)
Chromosomal abnormalities e.g. Klinefelter’s (XXY)
Hormonal problems e.g. hypogonadotropic hypogonadism
Lifestyle incl. stress, diet, alcohol, drugs, heat
what factors can affect sperm transport?
Infection/STIs can damage vas deferent, epididymis etc…
Congenital absence of vas deferens weirdly common in CF
Other tube blockages, including vasectomy
Tumours
possible causes of male sexual dysfunction resulting in infertility?
Retrograde ejaculation (back to bladder, often due to problem with circular muscle at base of bladder)
Spinal cord injury
Prostate surgery (damage of nerves/BVs needed for erection/ejaculation)
Some medicines, like antidepressants
varicocele - what is it? when does it occur? what is it caused by?
why does this cause infertility/low sperm count?
Enlargement of veins (pampiniform plexus) draining the deoxygenated blood from testes
Occurs when blood flows backwards into the internal spermatic vein resulting in vascular dilation of the veins in the pampiniform plexus
Caused by a congenital absence (or poorly functioning) valves in these veins, typically found on left side as here there is higher hydrostatic pressure owing to the perpendicular drainage of the left internal spermatic vein into the left renal vein. Plus the nutcracker effect - sup. Mesenteric artery crosses left renal vein exerting extra pressure
Why this causes infertility/low sperm count -
Possibly due to increased temperature of scrotum, increased concentration of toxic metabolites, greater levels of ROS
three main areas effected that cause infertility in women?
Oogenesis and ovulation issues
includes hormonal issues
oocyte/zygote transport/implantation
issues with pregnancy
how can age cause infertility?
partly due to natural reduction in ovarian reserve, but mostly due to a decline in quality…
oocytes begin meiosis in the foetus, but then enter a prolonged arrest that lasts until ovulation—often decades later.
During this arrest, chromosome structures can become compromised. For example, if there were too few or poorly positioned crossovers (chiasmata) to begin with, or if cohesion proteins that hold sister chromatids together degrade over time, the risk of segregation errors increases.
These issues can lead to nondisjunction or mis-segregation of chromosomes, contributing to infertility, miscarriage, or chromosomal abnormalities in embryos
possible hormonal issues that can result in female infertility?
Hormone imbalance e.g. PCOS
Thyroid - over/underactive, disrupts hormonal regulation of ovulation
Premature ovarian failure
Genetics - turner syndrome (X, impaired ovarian development)
what can cause issues with oocyte/zygote transport or implantation issues?
Tubal damage due to infection e.g. after caesarean, previous ectopic pregnancy.
Surgical damage during previous pregnancy
Endometriosis, fibroids. Make it difficult for implantation to succeed. Endo – epithelial cells lining the uterus start to grow outside the uterus. Fibroids = lumps of fibrous tissue in uterus get in way of implantation, removable tho
possible issues with pregnancy itself
Also more likely with age - For women under the age of 25 years ~2% of all clinically recognized pregnancies are trisomic. But for women aged 40 or over the proportion of pregnancies affected by trisomy increases to around 30%
Chromosomal abnormalities (more likely with age^)
Autoimmune conditions, antiphospholipid syndrome (by disrupting immune tolerance and increasing risk of clots) lupus (inflammation affecting placental function) and autoimmune thyroid disease
explain what PCOS is
Polycystic ovarian syndrome
Normally, each month, several half-developed oocytes begin to mature, and typically one is ovulated. In PCOS, a larger number of follicles are recruited, but they arrest in development and never reach maturity. This results in the appearance of ‘cysts’—actually these are the arrested, undeveloped follicles.
The problem is due to a hormonal imbalance: there’s an excess of LH and not enough FSH. LH stimulates theca cells, which expand and produce androgens (like testosterone). But without enough FSH, granulosa cells don’t develop properly, and the follicles can’t mature or produce the hormones needed for ovulation. This leads to over-recruitment but underdevelopment of follicles.
what symptoms can PCOS cause and how can this affect fertility?
The excess theca cells produce more testosterone, which can cause symptoms like acne and hirsutism (excess hair growth).
PCOS is also linked to insulin resistance and altered liver enzyme function, often contributing to weight gain.
Cycles are often irregular and don’t always result in ovulation
IVF - first done when? how successful is it according to the HFEA?
First IVF baby born in the uk in 1978
Relatively successful, pregnancy rates have increased across all ages in the last 30 years, In 18-34 year olds IVF is successful 40% of the time (2021) HFEA.
Though risen, the success rate is still low over 40)..
IVF - explain how it works in terms of getting the patient’s eggs and getting the patient ready for implantation
ovarian stimulation - Cocktail of drugs including FSH to get a load of follicles maturing at once The goal is to get more follicles to final maturation stage, want to harvest 15-16 mature oocytes
Must also suppress ovulation, as the eggs are retrieved from the ovaries. GnRH antagonists or agonists are often used to suppress the LH surge, which would otherwise trigger ovulation
When in the retrieved eggs are in culture, they are given more hormones for further maturation
Patient given hormones like oestrogen and progesterone to prep lining of uterus
second stage of IVF - fertilisation?
When the retrieved eggs are in culture, they are given more hormones for further maturation
Sperm sample - must be incubated in appropriate medium. Need to encourage capacitation as the female tract would.
Co-incubation – to allow fertilisation. Watched very carefully to see the development. Fertilised ones are separated and watched for normal development and cleavage
last stage of IVF - embryo transfer?
Day 5/6, blastocyst stage just before typical implantation time, they are put in uterus.
Implantation is not guaranteed so multiple (3-4) eggs used to be put in at once. But as multiple pregnancies are riskier for baby and mum especially, this happens less now, single embryo transfer often preferred.
what is in vitro maturation (IVM)?
Why is it useful?
The oocytes are collected before they are mature, and so are cultured in vitro in the presence of FSH and other factors before continuing with ICSI or IVF as normal
Benefits - women can avoid using all the drugs involved in IVF, which is very useful for women vulnerable to ovarian hyperstimulation syndrome, which makes patients systemically unwell. Rare, now less than 5% of cases, but still a problem, especially when its more likely in women with PCOS
what is ICSI?
ntracytoplasmic sperm injection
Becoming increasingly common. At first, success rates were lower than IVF
Rates have been improving
sperms/spermatids are directly injected into the egg cytoplasm
Fertilisation involves a lot of steps that are being bypassed
Non-motile sperm can be used (good if this is a cause of infertility)
Possibly higher rate of abnormalities in foetus
