SUBFERTILITY Flashcards
(145 cards)
1
Q
What is Subfertility?
A
This generally describes any form of reduced fertility that results in a prolonged duration of unwanted lack of conception
2
Q
What is infertility?
A
The period of time people have been trying to conceive without success, after which formal investigation is justified and possible treatment implemented
WHO define it as the failure to achieve a pregnancy after 12 months or more of regular unprotected intercourse
3
Q
Primary and secondary infertility?
A
Primary - couples who have never conceived
Secondary - in couples who have conceived at least once before with the same or a different sexual partner
4
Q
How common is infertility?
A
1 in 6 people of reproductive age worldwide
1 in 7 heterosexual couples in the UK
5
Q
How commonly is infertility investigated and no identifiable cause is found?
A
25% of couples
6
Q
4 main causes of infertility?
A
Factors in the man causing infertility - 30% of couples
Ovulatpry disorders - 25%
Tubal damage - 20%
Uterine or peritoneal disorders - 10%
7
Q
Group 1 ovulation disorders?
What does it include?
A
Caused by hypothalamic-pituitary failure
Includes: Hypothalamic amenorrhoea and hypogonadotropic hypogonadism
8
Q
Cause of hypothalamic amenorrhoea?
A
Commonly due to low body weight or excessive exercise
9
Q
What causes hypogonadotrophic hypogonadism?
A
Unknown in most cases
May be congenital e.g. kallman syndrome
10
Q
What are group 2 ovulation disorders?
A
Dysfunctions of the hypothalamic-pituitary-ovarian axis
E,g, hyperprolactinaemic amenorrhoea and PCOS
11
Q
Most common type of group 2 ovulation disorders?
A
PCOS
12
Q
What are group 3 ovulation disorders?
What are they characterised by?
A
Ovarian failure
Characterised by high gonadotrophins, hypogonadism and low oestrogen level
13
Q
What are causes of ovulatory disorders?
A
Group 1 ovulation disorders - hypothalamic-pituitary failure
Group 2 ovulation disorders - hypothalamic-pituitary-ovarian axis dysfunction
Group 3 ovulation disorders - ovarian failure
Hyperthyroidism and hypothyroidism
Cushing sundrome and congenital adrenal hyperplasia
Chronic debilitating diseases e.g. uncontrolled DM, cancer, AIDs, end-stage kidney disease, malabsorption
14
Q
How often are group 2 ovulation disorders (hypothalamic-pituitary-ovarian axis dysfunction) present in women with infertility?
A
In 85% of cases
15
Q
Most common cause of tubal factor infertility?
A
PID and acute salpingitis
16
Q
Causes of tubal damage that can lead to infertility?
A
PID - chlamydia, gonorrhoea and anaerobic organisms
Acute salpingitis
Appendicitis
Diverticulitis
Endometriosis - may cause anatomical obstruction with adhesions
Injury to fallopian tube during previous surgiers
Ischaemic nodules
Polyps or mucus
Tubal spasm
Congenitally abnormal tubes
Ashermans syndrome
Fibroids
17
Q
Uterine causes of infertility?
A
Adhesions
Polyps
Submucous leiomyomas
Septae
18
Q
Most common cause of infertility in men?
A
Primary testicular failure - due to oligozoospermia
19
Q
Causes of testicular failure?
A
Cryptorchidsm
Testicular torsion
Testicular trauma
Orchitis
Chromosomal disorders e.g. Klinefelter syndrome
Systemic disease
Radiotherapy or chemotherapy
Varicoceles
20
Q
What is obstructive azoospermia?
A
the absence of spermatozoa in the sediment of a centrifuged sample of ejaculate due to obstruction
21
Q
What can cause obstructive azoospermia?
A
Congenital e.g. congenital bilateral absence of vascular deferens, mullerian cysts
Acquired secondary to epididymal or prostatic infections, vasectomy or complications of surgical procedures
Cystic fibrosis
22
Q
What is non-obstructive azoospermis caused vt?
A
Testicular failure
23
Q
Causes of infertility in men?
A
Testicular failure
Obstructive azoospermia
Ejaculatory and ED
Abnormal sperm function and quality
Unexplained cause
24
Q
Ejaculatory disorders?
A
Premature ejaculation.
Delayed ejaculation.
Retrograde ejaculation (semen passing backwards into the bladder).
Anejaculation (no ejaculation).
Painful ejaculation.
Anorgasmia (perceived absence of orgasm, which can give rise to anejaculation).
Haematospermia (blood in the ejaculate, which may indicate underlying pathology).
25
Definition of erectile dysfunction?
persistent inability to attain and maintain an erection sufficient to permit satisfactory sexual performance
26
Associations with erectile and Ejaculatory dysfunction?
Psychological factors
Hypogonadism
Spinal cord disease
Metabolic and vascular conditions e.g. diabetes
Lifestyle factors e.g. smoking, alcohol, obesity
Use of certain drugs
27
Causes of reduced sperm motility?
Kartagener syndrome
Antisperm antibodies
28
What can affect sperm function and quality?
Kartagener syndrome and antisperm antibodies
Urogenital tract infections
Anabolic steroids
29
Risk factors for infertility in women?
Age
STIs - can damage genital anatomy
Obesity
Low body weight
Lifestyle - smoking, stress
Occupation and environment - pesticides, NO exposure, metals, solvents, formaldehyde
Drugs - NSAIDs, chemotherapy, antipsychotics, sertraline, fluoxetine, metoclopramide and methyldopa which can increase prolactin levels
Recreational drugs
30
Risk factors for infertility in men?
Age
STIs
Obesity
Lifestyle - smoking, alcohol,stress
Occupation and environment - pesticides, NO, metals, solvents, formaldehyde
Tight underwear - elevated scrotal temperature and reduced semen quality link?
Medicines
Recreational drugs e/g/ anabolic steroids and cocaine
31
Medications that can interfere with fertility in men?
Sulfasalazine and some antifungal treatments can adversely affect spermatogenesis.
Certain antipsychotics, antidepressants, and antihypertensives can cause retrograde ejaculation and orgasmic dysfunction.
Long-term opiate use can cause hormonal dysregulation and impair bulk semen parameters.
5-alpha reductase inhibitors can cause sexual dysfunction.
Finasteride may impair semen parameters.
Hormone treatment, particularly testosterone supplementation or anabolic steroid treatment, can inhibit spermatogenesis and impair fertility.
32
Complications of asssited conception?
Ovarian hyperstimulation syndrome
Ectopic pregnancy
Pelvic infection
Multiple births
33
How often is it recommended to have sexual intercourse when trying to conceive?
Every 2-3 days
34
Physical examination for women concerned about infertility?
BMI
Look for hirsutism and acne - PCOS
Look for galactorrhoea - hyperprolactinaemia
Abdominal examination - masses?
Pelvic examination - infection or tenderness?
Vaginal examination - undisclosed sexual diffiuclties e.g. vaginismus
35
Physical examination for men concerned about infertility?
Examine the penis, including a check of the position of the urethral meatus, for structural abnormalities.
Examine the scrotum and testicles for lumps (which may indicate varicocele, hernia, or cancer); small, soft testes (which may indicate hypogonadism); or undescended testes.
Assess secondary sexual characteristics. In hypogonadism, there may be a decrease in beard and body hair growth and a decrease in muscle mass.
Look for gynaecomastia, which may indicate hypogonadism.
36
What % of couples in the general population will conceived within 1 year if the woman is under 40 and there is regular unprotected intercourse?
80%
Half of those who dont will do so in the second year. Cumulative pregnancy rate of >90%
37
How does artificial insemination affect chances of conception?
over 50% of women under 40 years old will conceive within 6 cycles of intrauterine insemination.
About half of those who do not conceive within 6 cycles of IUI will do so with a further 6 cycles = cumulative pregnancy rate over 75%
38
When should you start investigating for a cause of infertility?
In couples after 1 year of regular unprotected intercourse
Or earlier to couples that are identified as less likely to conceive
39
How do we confirm ovulation in women?
Measure mid-luteal progesterone (day 21 or a 28 day cycle)
40
Initial investigations for infertility in women?
Mid-literal phase progesterone day 21 of a day 28 cycle
Screen for chlamydia
Gonadotropin measurements in women with irregular menstruation - to identify ovulation disorders
Thyroid function tests
Prolactin measurement in women with symptoms of an ovulation disorder, galactorrohoea or suspected pituitary tumour
41
Initial investigations for infertility in men?
Semen analysis - analyse using WHO reference ranges!
Screen for chlamydia
42
When can a semen specimen be collected for semen analysis?
After at least 2 days and max 7 days of sexual abstinence
43
Where should the semen specimen for semen analysis be collected and why?
In a private room never the lab to avoid exposure of the semen sample to fluctuations in temperature and control the time between collection and analysis
Preferably within 30 mins and at least no longer than 50 mins after collection!
44
What should you do if semen analysis shows abnormalities?
Repeat test 3 months later to allow time for the cycle of spermatozoa to be completed
After 2 abnormal semen examination results send to secondary care for further assessment
45
When should you refer a couple for additional investigations and management in those presenting with infertility?
If history, exam and investigations are normal in both partners, the couple has not conceived after 1 year and the woman is younger than 36
Consider earlier if:
Women - 36 or older (refer at 6 months), amenorrhoea/oligomenorrhoea, previous pelvic/abdo surgery, previous PID, previous STI, abnormal pelvic exam, known reason for infertility
Men - previous genital pathology, previous urogenital surgery, previous STI, varicocele, significant systemic illness, abnormal genital exam, 2 abnormal semen analysis results, known reason for infertility
46
When should couples undergoing investigation for infertility be offered counselling?
Before, during and after investigations and Tx regardless of the outcome!
47
Following referral what additional investigations might couples with ?infertility undergo?
Tubal patency tests in women - hysterosalpingography, hysterosalpingo-contrast ultrasonography, or diagnostic laparoscopy and dye
Assessment of sperm - microbiological tests, sperm culture, endocrine tests, imaging of urogenital tract and testicular biopsy
48
Why is timed intercourse to coincide with ovulation not recommended?
As it can lead to stress and pressure in the relationship
49
What could High FSH in a woman struggling to conceive indicate?
Poor ovarian reserve - the pituitary is producing extra FSH in an attempt to stimulate follicular development
50
What could High LH in a woman struggling to conceive indicate?
PCOS
51
What hormone can be measured and is the most accurate marker of ovarian reserve?
Anti-mullerian hormone
It is released by granulosa cells in the follicles and falls as eggs are depleted
52
What is a hysterosalpingogram?
What happens?
What are the risks?
a type of scan used to assess the shape of the uterus and the patency of the fallopian tubes.
It has a diagnostic and therapeutic benefit! It seems to increase the rate of conception without any other intervention. Tubal cannulation under xray guidance can be performed during the procedure to open up the tubes.
What happens?
A small tube is inserted into the cervix. A contrast medium is injected through the tube and fills the uterine cavity and fallopian tubes. Xray images are taken, and the contrast shows up on the xray giving an outline of the uterus and tubes. If the dye does not fill one of the tubes, this will be seen on an xray and suggests a tubal obstruction.
What are the risks?
There is a risk of infection with the procedure, and often antibiotics are given prophylactically for patients with dilated tubes or a history of pelvic infection. Screening for chlamydia and gonorrhoea should be done before the procedure.
53
Key counselling points for couples trying to conceive?
folic acid
aim for BMI 20-25
advise regular sexual intercourse every 2 to 3 days
smoking/drinking advice
54
What level of serum progesterone indicates ovulation?
>=30
55
What % of infertility causes are caused by male issues?
30%
56
3 types of fertility treatment options?
Medical treatment
Surgical
Assisted reproduction techniques
57
Medical treatment to restore fertility in cases where there is anovulation?
Clomifene (anti-oestrogen drug) - to stimulate ovulation
Gonadotrophins may be used in clomifene-resistance anovulatory infertility - these stimulate ovulation
Pulsation GnRH and dopamine agonists
58
How does clomifene work and when is it given for anovulation?
A selective oestrogen receptor modulator. It stops the negative feedback of oestrogen on the hypothalamus, resulting in a greater release of GnRH and subsequently FSH and LH
Given on days 2-6 of the menstrual cycle
59
Surgical option for managing anovulation in cases of PCOS?
Ovarian drilling under laparoscopic surgery
The surgeon punctures multiple holes in the ovaries using diathermy or laser therapy. This can improve the woman’s hormonal profile and result in regular ovulation and fertility.
60
Sugrical treatment options to restore fertility?
Tubal microsurgery - tubal catheterisation or cannulation for proximal tubal obstruction
Sugrical ablation/resection of endometriosis + laparoscopic adhesiolysis
Surgical correction of epididymal blockage in men with obstructive azoospermia
61
Assisted reproduction technique options?
Intrauterine insemination
In vitro fertilisation
Intracytoplasmic sperm injection
Donor insemination
Oocyte donation
62
What is the Human Fertilisation and EMbryology Authority?
The HFEA is responsible for regulating all NHS and private clinics offering infertility treatments to ensure compliance with the Human Fertilisation and Embryology Act 1990.
63
What is intrauterine insemination?
in this process, which is timed to coincide with ovulation, sperm is placed in the woman's uterus using a fine plastic tube. Low doses of ovary-stimulating hormones (oral anti-oestrogens or gonadotrophins) might be given (stimulated IUI) to maximize pregnancy rates.
64
What is in vitro fertilisation?
involves retrieval of one or more ova combined with sperm and incubated for 2–3 days; the resultant embryo is then injected into the uterus via the cervix. This method is suitable for women who have blocked fallopian tubes, men with a minor degree of subfertility, and couples who have been diagnosed with unexplained infertility or have been unsuccessful with other techniques (such as ovulation induction or IUI).
65
What is intracytoplasmic sperm injection?
It’s add on for IVF
the sperm of highest quality is inserted directly into the egg cytoplasm using a micropipette. The fertilised embryo is subsequently reintroduced into the uterus of the child-carrying party
This allows for fertilisation in cases were sperm mobility may be severely compromised or where the egg zona pellucida may be difficult to penetrate e.g. when using eggs previously frozen.
66
What is a donor insemination?
involves insemination of sperm, from a donor, into a woman via her vagina into the cervical canal or into the uterus itself (IUI). This method is considered when the man has no (or very few) sperm on testicular biopsy or surgical extraction, has had a vasectomy and reversal has failed or not been tried, or has an infectious disease (such as HIV), or where there is a high risk of transmitting a genetic disorder to the offspring. It is also considered in couples where there is no male partner.
67
What is oocyte donation?
involves stimulation of the donor's ovaries and collection of ova. The donated ova are then fertilized by the recipient's partner's sperm. After 2–3 days, the embryos are transferred to the uterus of the recipient via the cervix after hormonal preparation of the endometrium. This method is considered for women with ovarian failure (premature or after radiotherapy or chemotherapy); those with bilateral oophorectomy; those with gonadal dysgenesis, including Turner's syndrome; and when the risk of transmitting a genetic disorder is high. It is also used in certain cases of IVF failure.
Couples who have had successful IVF or ICSI may decide to donate their spare embryos to help other infertile couples (embryo donation).
68
Symptoms of ovarian hyperstimulation syndrome?
Mild — abdominal bloating and mild abdominal pain.
Moderate — nausea and vomiting and increased abdominal discomfort.
Severe — oliguria, generalized oedema, abdominal pain and/or distension (caused by enlarged ovaries and acute ascites), and hydrothorax (occasionally).
Critical — oligo/anuria, tense ascites or large hydrothorax, thromboembolism, and acute respiratory distress syndrome.
69
What is ovarian hyperstimulation syndrome?
A complication seen in some forms of infertility Tx
The presence of multiple luteinized cysts within the ovaries results in high levels of vasoactive substances e.g. vascular endothelial growth factor, which are released by granulosa cells of the follicles. This results in increased membrane permeability and loss of fluid from the intravascular compartment = ascites, oedema, hypovolaemia
70
Which fertility treatments have the higher risk of ovarian hyperstimulation syndrome?
Gonadotropins - development of multiple follicles
hCG treatment - provokes by the “trigger injection” 36 hours before oocyte collection as it stimulates release of VEGF from follicles
IVF - 1/3rd of women have mild OHSS
71
How do we prevent ovarian hyperstimulation syndrome?
During stimulation with gonadotrophins, 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)
In women at higher risk several strategies may be used to reduce the risk:
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)
72
Management of ovarian hyperstimulation syndrome?
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)
Often managed as an outpatient. Severe cases may require admission and critical cases may need ICU
73
How could you monitor th volume of fluid in the intravascular space?
Monitoring haematocrit as its the concentration of RBC in the blood so when it goes up it indicates less fluid in the intravascular space
Raised haematocrit may indicate dehydration!
74
Instructions for men when providing a semen sample for analysis?
Abstain from ejaculation for at least 3 days and at most 7 days
Avoid hot baths, sauna and tight underwear during the lead up to providing a sample
Catch the entire sample
Deliver the sample to the lab within 50 mins of ejaculation (30 is better)
Keep the sample warm (e.g. in underwear) before delivery
75
What is checked for in semen analysis?
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%)
76
What is polyspermia/polyzoospermia)?
High number of sperm in semen sample
>250 million per ml
77
What is normospermia?
Normal characteristics of sperm in the semen sample
78
What is oligospermia?
Reduced number of sperm in the semen sample:
Mild 10-15 million/ml
Moderate 5-10 mil/ml
Severe <5mil/ml
79
What is cryptozoospermia?
Very few sperm in the semen sample
<1 million per ml
80
What is azoospermia?
Absence of sperm in the semen
81
Causes of hypogonadotrophic hypogonadism in men?
Pathology of pituitary gland or hypothalamus
Suppression due to stress, chronic conditions or hyperprolactinaemia
Kallmann syndrome
82
What can cause testicular damage that can result in defective sperm production?
Mumps
Cryptoorchodism
Trauma
Radiotherapy or chemotherapy
Cancer
83
What genetic or congenital conditions can result in defective sperm production?
Klinefelter syndrome
Y chromosome deletions
Sertoli cell-only syndrome
Anorchia
84
What can cause obstruction to sperm being ejaculated?
Damage to the testicle or vas deferens - trauma, surgery or cancer
Ejaculatory duct obstruction
Retrograde ejaculation
Scarring from epididymitis
Absence of vas deferens e.g. in CF
Young’s syndrome
85
What is the triad in young’s syndrome?
Obstructive azoospermia
Bronchiectasis
Rhinosinusitis
86
What is fecundicity?
The capacity to have a live birth
87
What is fecundability?
The probability of achieving a pregnancy that results in a live birth in a single menstrual cycle with adequate sperm exposure and no contraception
88
What is sterility?
The permenant state of infertility
89
Why is addressing infertility important?
It affects millions of people worldwide
Every human has the right to the enjoyment of the highest attainable standard of physical/mental health
Individuals and couples have the right to decide the number, timing and spacing of their children
Heterosexual couples, homosexual couples, older people, individuals not in sexual relationships and those with certain medical conditions should be able to have fertility care service access
Infertility can have significant negative social impacts - divorce, violence, social stigma, emotional stress, depression, anxiety, low self-esteem
Addressing infertility can mitigate gender inequality. Although both women and men can experience infertility, women in a. Relationship with a man after often perceived to suffer the infertility. It has negative social impacts on the lives of couples, especially women e.g. violence, domestic abuse, emotional stress, low self-esteem, divorce
The fear of infertility can deter women and men from using contraception if they feel social pressure to prove their fertility at an early age
90
What does a rise in progesterone on day 21 indicate?
That ovulation has occurred and the corpus luteum has formed and started secreting progesterone
91
What is the laparoscopy and dye test?
Laparoscopic procedure where dye is injected into the uterus and should be seen entering the fallopian tubes and spilling out at the ends
If tubal obstruction this will not be seen
Surgeon can also assess/treat endometriosis or pelvic adhesions
92
Structure of IVF access on the NHS
The provision of IVF treatment varies across the country, and often dependas on local integrated care board policies
ICBs may have additional criteria needed to be met before the couples can have IVF on the NHS e.g. not having any childen already, being a healthy weight, not smoking, under 35 years old
NICE recommend up to 3 cycles of IVF to be offered on the NHS but some ICBs only offer 1 cycle or only offer NHS_funded IVF in exceptional circumstances
93
NICE recommendations for IVF for women under 40?
Under 40 + trying to get pregnant through regular unprotected sex for 2 years + not been able to get pregnant after 12 cycles of artificial insemination with at leats 6 of the cycles being with intrauterine insemination = 3 cycles
94
NICE recommendations for IVF for women 40-42?
40-42
Been trying to get pregnant through regular unprotected sex for 2 years or after 12 cycles of artificial insemination with at least 6 of the cycles using intrauterine insemination + never had IVF treatment before + show no evidence of low ovarian reserve + they’ve been informed of the additional implications of IVF and pregnancy at this age
95
Cost of IVF in a private clinic?
Cost can vary but 1 cycle can be up to 5000 pounds or more
96
Pros of IVF
Helps many pt who would otherwise be unable to conceive
Can be more successful than IUI and other forms of ART
Can help single women and same sex couples
Allows for pre-implantation genetic diagnosis - tested for over 600 conditions so really useful for pt who have terminated pregnancies as a result of serious genetic disease or those with PMH or FHx of it
Unused embryos can be donated to research or another couple
97
Disadvantages of IVF
May be unsuccessful
Small chance of side effects e.g. hot flushes, headaches, ovarian hyper-stimulation syndrome
Multiple pregnancy risk of up to 30% - increases risk of miscarriage, pre-eclampsia, gestational diabetes, c-section requirement etc
Slightly higher than of ectopic pregnancy
May be a link to increased risk of prematurity and LBW
Emotional and psychological impact
Expensive or may not have access
Ethical issues
98
In which women with IVF should double embryo transfers be considered?
In women aged 40-42
Younger women should only be considered for it if there are no top-quality embryos to choose from
99
What is surrogacy?
The process of a 3rd party carrying a foetus for another couple
May be appropriate option for couples without a uterus e.g. same sex couples, those with uterine abnormalities and those who have suffered multiple miscarriage and failed IVF implantations
100
2 types of surrogacy?
Full surrogacy - the party carrying the foetus is not genetically relayed to the implanted foetus “host surrogacy”
Partial surrogacy - surrogates egg is fertilitsed via IVF and then re-implantated
101
Laws around surrogacy?
By law the party giving birth to the child is its legal mother
Patients pursuing this option are strongly advised to seek legal counsel prior to commencing the procedure
102
Roles of parents
Provide a home for the child
Protect and maintain the child
They are also responsible for:
disciplining the child
choosing and providing for the child’s education
agreeing to the child’s medical treatment
naming the child and agreeing to any change of name
looking after the child’s property
103
Relationship between weight and fertility?
BMI >=30 - likely take longer to conceive
BMI >=30 who are not ovulation - losing weight is likely to increase their chances of conception
BMI <19 with amenorrhoea or oligomenorrhoea - increasing body weight is likely to improve chance of conception
Men with BMI >=30 are likely to have reduced fertility
104
If you are considering obstructive azoospermia, what genetic testing should you do?
Cystic fibrosis
microdeletion of Y chromosome
105
What % of men with cystic fibrosis are infertile?
98%
106
What is the ultimate marker of ovarian reserve?
Age
In general, older women with good reserve are likely to do less well in IVF than younger women with poor reserve
107
What is controlled ovarian hyperstimulation?
Who is it for?
The process of inducing a woman to release >1 egg a month
Treatment for women with hypogonadotrophic hypogonadism or PCOS, or PCOS with failed clomphene treatment
108
How successful is ovarian drilling in PCOS/
80% of pt who undergo ovarian drilling resume ovulation
Nearly 50% are able to get pregnant within 1 year
Its also less likely to produce a multiple pregnancy compared to other fertility Tx
109
Steps of an IVF treatment cycle?
Hormone stimulation
Sperm collection
Oocyte retrieval
Embryo culture
Embryo transfer
110
How is egg retrieval done in IVF?
Under US guidance, a needle is inserted through the vaginal wall and into an ovarian follicle. Once the folllicle is entered, suction is gently applied to aspirate follicular fluid and with it cellular material including the oocyte
111
How is embryo transfer done in IVF?
It’s performed either at the cleavage stage (day 2-4) or the blastocyst stage (day 5-6)
A soft transfer catheter is loaded with the embryo and is inserted through the cervical canal and advanced into the uterine cavity
Correct placement is 1-2cm from the uterine fundus
112
The challenges of infertility?
Availability, access and quality of interventions to address infertility remain a challenge in most countries
Diagnosis and Tx is often not prioritised in national population and development policies and reproductive health strategies
Rarely covered in public health financing
Lack of trained personnel and the necessary equipment and infrastructure
High costs of treatment medications
This is all particularly prevalent in LMIC
113
How to address the issues of infertility?
Government policies for access to safe and effective fertility care
Recognising infertility is a disease that can often be prevented - this mitigates the need for costly and poorly accessible treatments
Incorporating fertility awareness in national comprehensive sexuality education programmes
Enabling laws and policies that regulate third party reproduction and ART to ensure universal access without discrimination and to protect human rights of all parties involves
Monitoring of the quality of fertility policies and services and ensuring they continually improve
114
WHO response to challenges of infertility?
Conduction of global epidemiological and etiological research into infertility.
Engaging and facilitating policy dialogue with countries worldwide to frame infertility within an enabling legal and policy environment.
Supporting the generation of data on the burden of infertility to inform resource allocation and provision of services.
Developing guidelines on the prevention, diagnosis and treatment of male + female infertility
Continually revising and updating other normative products, e.g. laboratory manual for the examination and processing of human semen.
Collaborating with relevant stakeholders to strengthen political commitment, availability and health system capacity to deliver fertility care globally.
Providing country-level technical support to member states to develop or strengthen implementation of national fertility policies and services.
115
Nutrition and fertility
Men - Diet rich in carbs, fiber, folate, lycopene, fruit. Low protein and fats
Women - Vegetable protein is better than animal protein, low trans fat, multivitamins and iron - beneficial
Antioxidants to remove ROS
116
Exercise and fertility link?
A healthy amount of exercise is beneficial
Men who exercise at least 3 times a week for 1 hour have better sperm
Excessive exercise in women can negatively alter the enrgey balance and result in hypothalamic dysfunction
117
How does smoking affect fertility?
Men who smoke tend to have decreased total sperm count, density, motility, morphology, semen volume, fertilising capacity
Women who smoked have significantly higher odds of infertility - may reduce ovarian resrve?
118
Link between alcohol and fertility?
In men alcohol consumption is linked to testicular atrophy, decreased libido and decreased sperm count
Women who drink large amounts of alcohol have a higher chance of experiencing infertility than monderate or low drinkers
119
Link between caffeine and fertility?
Caffeine has been associated with an increase in time to pregnancy of over 9.5 months, particularly if amount is >500mg per day. Also increases risk of miscarriage and spontaneous abortion in the first trimester
120
What are some of the responsibilities parents may have to consider before deciding to adopt a child?
Legal eligibility criteria + undergo the assessment process
Emotional and financial stability
You must have a fixed home in the UK, channel island or Isle of Man and have lived there for at least 1 years
You must be 21
Demonstrate a commitment to the well-being and best interests of the child
Be well informed about the adoption process
Demonstrate parenting skills and readiness
Maintain good physical and mental health
Have a reliable support system e.g. family and friends
Be sensitive to the child’s cultural background
Attend required adoption educationa nd training programmes
Be open to maintaining contact with the child’s birth family if deemed in the best interests of the child
Be prepared for a lifelong commitment to the adopted child
Support the child in building relationships with peers and integrating into the community
121
What are the female factors affecting fertilisation?
Hormones
Oogenesis
Implantation
Potential for pregnancy
122
What are the male factors affecting fertilisation?
Hormones
Spermatogenesis
Maintaining an erection
Ejaculation
123
Chance of getting pregnant in a fertile couple after 1 month of unprotected sex?
20%
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What are the 2 protocol options for suppressing the natural menstrual cycle for IVF?
For the GnRH agonist protocol, an injection of a GnRH agonist is given in the luteal phase of the menstrual cycle, around 7 days before the expected onset of the menstrual period. This initially stimulates the pituitary gland to secrete a large amount of FSH and LH. However, after this initial surge in FSH and LH, there is negative feedback to the hypothalamus, and the natural production of GnRH is suppressed. This causes suppression of the menstrual cycle.
For the GnRH antagonist protocol, daily subcutaneous injections of a GnRH antagonist are given, starting from day 5 – 6 of ovarian stimulation. This suppresses the body releasing LH and causing ovulation to occur.
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Why is it important to suppress the natural menstrual cycle?
Without doing it, ovulation would occur and the follicles that are developing would be released before it’s possible to collect them
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How is ovarian stimulation done in IVF?
From about day 2 of the cycle… Subcut injections of FSH over 10-14 days to stimulate follicular development
Close monitoring with regular TVUS. When enough follicles are an adequate size FSH is stopped and hCG injection is given to stimulate final maturation of follicles “trigger injection”. After 36 hours eggs are collected
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How is oocyte collection done in IVF?
Oocyte are collected from ovaries under guidance of TVUS.
A needle is inserted through the vaginal wall into each ovary to aspirate the fluid from each follicle. This fluid contains the mature oocytes from the follicles. The procedure is usually performed under sedation (not a GA). The fluid from the follicles is examined under the microscope for oocytes.
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How is oocyte insemination done in IVF
The male produces a semen sample around the time of oocyte collection. Frozen sperm from earlier samples may be used. The 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.
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Embryo culture in IVF?
Dishes containing the fertilised eggs are left in an incubator and observed over 2 – 5 days to see which will develop and grow. They are monitored until they reach the blastocyst stage of development (around day 5).
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What happens to remaining embryos from IVF?
Can be frozen for future attempts at transfer
Can be donated
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What happens after embryo transfer in IVF?
Pregnancy test at day 16 after egg collection. If positive = implantation occurred
If negative then its failed and hormonal Tx is stopped and women will have a menstrual period (likely more bleeding than usual)
Progesterone (vaginal) is used from the time of oocyte collection until 8 – 10 weeks gestation. This is to mimic the progesterone that would be released by the corpus luteum during a typical pregnancy. After this the placenta takes over, and the suppositories are stopped.
An USS is performed around 7 weeks to check for a fetal heartbeat, and rule out miscarriage or ectopic pregnancy. When the USS confirms a health pregnancy, the remainder of the pregnancy can proceed with standard care, as with any other pregnancy.
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Complications of egg collection procedure in IVF?
Pain
Bleeding
Pelvic infection
Damage to the bladder or bowel
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What is premature ovarian insufficiency?
How common?
The onset of menopausal symptoms and elevated gonadotropin levels before the age of 40. Due to a decline in the normal activity of the ovaries at an early age
1 in 100 women
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What is premature ovarian insufficiency characterised by?
Hypergonadootrophic hypogonadism - under activity of gonads -> lack of negative feedback on pituitary -> excess gonadotrophins
Raised LH and FSH
Low oestradiol
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Most common cause of premature ovarian insufficiency?
Idiopathic - may be FHx
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Causes of premature ovarian insufficiency?
Idiopathic
Bilateral oophorectomy
Radiotherapy/chemotheray
Infection eg. Mumps, TB, CMV
Autoimmune disorders e.g. Coelaic, DM, thyroid disease
Resistance ovary syndrome due to FSH receptor abnormalities
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Features of premature ovarian insufficiency?
Climacteric Sx - hot flushes, night sweats, vaginal dryness
Infertility
Secondary amenorrhoea
Raised FSH and LH shown on 2 samples 4-6 weeks apart
Low oestradiol
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NICE guidelines on diagnosing premature ovarian insufficiency?
Women under 40 with typical menopausal symptoms and elevated FSH on 2 consecutive samples 4-6 weeks apart
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Risks of premature ovarian failure?
higher risk of multiple conditions relating to the lack of oestrogen, including:
Cardiovascular disease
Stroke
Osteoporosis
Cognitive impairment
Dementia
Parkinsonism
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Management of premature ovarian failure?
HRT or COCP (less stigma + contraception in case ovarian function returns) should be offered to women until the age of the average menopause (51 years)
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Risks of HRT before age of 50
Not considered to increase risk of breast cancer as women would originally produce these hormones
Increased risk of VTE - can be reduced by transdermal methods
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What is the ‘postcode lottery’ in fertility services?
NICE state that the NHS should offer women under 40 3 full cycles of IVF if they have been trying for a child for more than 2 years. However, the number of CCGs offering the recommended 3 full IVF cycles to women under 40 is very low- only 12%
This is the case because each CCG, of which there are 207 in the country, is able to make individual decisions on whether to fund IVF treatment – they are able to set their own limit on the number of IVF cycles and their own criteria such as female age ranges.
Therefore, depending on where your GP is located, you may be entitled to less or more NHS funded IVF cycles, thus creating a further barrier for those suffering from infertility.
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Ethical issues of assisted conception
When does personhood begin? Conception? When viable?
Multiple pregnancies common which pose health risks to mother and foetus
Rights of donors, identity of biological parents and potential psychological impact on children through assisted reproduction
Surrogate mother exploitation, commodification of pregnancy, emotional/psycholgoical risks of all parties
Selection of embryos based on desired genetic traits - potential discrimination against indicviudals with genetic conditions
Commercialisation of reproductive technologies
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Issues with this statement “ women should not be provided with treatment unless account has been taken of welfare of any child who may be born as a result, including need for a father”
Welfare of child isnt defined
Not fair as doesnt need to meet criteria for a fertile couple to reproduce
Difficult to accurately predict welfare
You dont always need a father to flourish! There was a 2008 revision to “need for supportive parenting”
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The debate on assisted reproductive technology?
For: procreative autonomy, equity and child welfare in the case of pre-implantation genetic diagnosis (non-maleficience)
Against: involves destruction of human embryos, harmful to those trying to conceive as only 30% success rate, unnatural, expensive
