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Fertility Flashcards

1
Q

How common is subfertility?

A

• Subfertility is very common – with 1 in 6 couples seeking specialist help.

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2
Q

How likely is it a couple will conceive within 1 year? 2 years?

A

• People concerned should be informed that 80% of couples in general population will conceive within one year if:
o Woman <40, do not use contraception, regular sexual intercourse (every 2-3 days)
o About half will conceive in 2nd year

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3
Q

Causes of subfertility?

A
  • Ovulation disorder (21%)
  • Tubal factor (15-20%)
  • Male factor (25%)
  • Unexplained (28%)
  • Endometriosis (6-8%)
  • Sexual dysfunction (4-5%)
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4
Q

Causes of primary ovulation disorder infertility?

A

 Premature ovarian syndrome
 Genetic (Turner’s syndrome – 45X0; hypergonadotrophic hypogonadism)
 Autoimmune
 Iatrogenic (surgery, chemo)

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5
Q

Causes of secondary ovulation disorder infertility?

A

 PCOS
 Excessive weight loss or exercise
 Hypopituitarism (tumour, trauma, surgery)
 Kallman’s syndrome (anosmia; hypogonadotrophic hypogonadism)
 Hyperprolactinaemia

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6
Q

Causes of tubal factor infertility?

A 
o	PID, pelvic infection, miscarriage
o	STIs
o	Female sterilisation
o	Bicornuate uterus
o	Fibroids
o	Hostile cervical mucous
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7
Q 
Important points in female infertility history to consider in:
General health
Infertility history
Menstrual history
Sexual history
PMH
Drugs
A 
General Health
o	Smoking (stop), alcohol (reduce), recreational drug (avoid), BMI (aim for normal)

Infertility History
o Age, duration of subfertility, coital frequency & problems, any previous pregnancies in either partner, Hx of ectopic/tubal/pelvic surgery

Menstrual History
o Menstrual cycle regularity and LMP (? pregnant), pelvic pain (dysmenorrhoea, dyspareunia)

Sexual History
o Cervical smear history, previous/current STI/PID

PMH
o Any relevant medical or surgical history, CKD, DM, anorexia

Drug history (any prescription drugs that may be contraindicated in pregnancy and recreational drug use)

Folic acid

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8
Q

Examination performed in infertility female?

A 
General:
	BMI
	Signs of endocrine disorder:
•	Hyperandrogenism (acne, hairgrowth, alopecia), acanthosis nigricans, thyroid disease
	Visual field defects (?prolactinoma)

Pelvic:
 Exclude obvious pelvic pathology (adenexal masses, uterine fibroid, endometriosis [painful fixed uterus], vaginismus)
 Cervical smear
 Chlamydia screening

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9
Q

When to offer investigations in subfertile woman?

A

• Offer investigation after 1 year of trying (earlier if female and >35, amenorrhoea, oligomenorrhoea, past PID, past cancer Rx)

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10
Q

Primary care investigations of subfertility?

A

o Chlamydia & Rubella screening
o Mid-luteal progesterone level (on day 21 of 28-day cycle, to confirm ovulation >30 nmol/L)
o Baseline (day 2 – 5) hormone profile including FSH (high in POF, low in hypopituitarism), LH
o TFT
o Prolactin

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11
Q

Secondary care referred indicated when?

A

o Refer when woman >36, known cause of infertility, Hx of risk factors, investigations show apparent no chance of pregnancy with expectant management
o Specialist clinic.

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12
Q

Investigations performed when assessing uterine/ovarian structure in female subfertility?

A

 Pelvic USS
• Every woman – looks at uterus (shape, septum, endometrium, fibroids and polyps), ovaries (shape, present, PCOS)

 Hysteroscopy
• If abnormal USS, gold standard for uterine anomalies
• Can look for fibroids, polyps, adhesions, septae

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13
Q

Investigations used when assessing tubal patency in female subfertility? How and when?

A

 Hysterosalpingogram (HSG)
• Uses X-ray and contrast injected through cannula in cervix to demonstrate uterine anatomy and tubal patency
• Women with no known comorbidities (PID, ectopic pregnancy, endometriosis)
• Only perform if chlamydia swabs negative and give azithromycin 1g PO stat

 Laparoscopy and dye test
• Day case procedure which can be combine with a hysteroscopy to assess the uterine cavity is necessary.
• Gold standard for tubal patency and used 1st when pelvic comorbidities (can be diagnosed and treated) and 2nd line if HSG abnormal
• Requires GA

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14
Q

What is ovarian reserve testing? When used?

A

• Ovarian Reserve Testing (Pre-IVF)
o Measured around Day 3 of menstrual cycle – predict likely response to gonadotrophin stimulation in IVF
o Anti-Mullerian hormone ≤5.4pmol/L low and ≥25pmol/L for high
o Total antral follicle ≤4 for low response and >16 for high response
o FSH >8.9 for low and <4 for high

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15
Q

Lifestyle modification in female subfertility?

A

Healthy diet, stop smoking/recreational drug, reduce alcohol consumption, regular exercise

Folic acid 0.4mg/d
- 5mg/d - previous child with neural tube defect, personal or family history of neural tube defect, DM1/2, coeliac disease, BMI >30, thalassaemia

Avoid timed intercourse (recommend every 2-3 days)

Avoid ovulation induction kits/basal temperature measurements (no evidence of success and stressful)

Vitamin D 10mcg/d

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16
Q

Psychological management of female subfertility?

A
  • Subfertility and its management can be very distressing.
  • Some treatments have side effects and are not guaranteed to be successful.
  • The stress of this and disappointment of failed treatment needs to be addressed.
  • Couples should be offered counselling before and after treatment, along with information regarding patient support groups
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17
Q

Ovulation induction techniques used in female subfertility?

A

Weight loss/gain as appropriate.
Anti-oestrogens (e.g. Clomifene 50mg days 2-6)
Gonadotrophins or pulsatile GnRH
Laparoscopic ovarian diathermy
Insulin sensitizers (Metformin)
Surgery
Assisted reproduction (IUI/IVF/oocyte donation)

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18
Q

When are ovulation induction agents used mostly?

A

PCOS
If ovulation at any time - await natural conception (IVF if no pregnancy in 6-9 cycles)

If no ovulation:
Lose weight
Clomifene
GnRHs
Laparoscopic ovarian diathermy
Metformin used alongside

If no pregnancy in 6-9 cycles then offer IVF

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19
Q

Surgical management of female subfertility?

A

 Preferably laparoscopic
 Treat endometriosis (laser/diathermy/excision)
 Tubal surgery (microsurgery/adhesiolysis)

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20
Q

How common is male subfertilty?

A

• Accounts for 20-25% of cases of subfertile couples.

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21
Q

How likely are a couple to conceive with 1 year? 2 year?

A

• People concerned should be informed that 80% of couples in general population will conceive within one year if:
o Woman <40, do not use contraception, regular sexual intercourse (every 2-3 days)
o About half will conceive in 2nd year

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22
Q

What is male fertility dependent on?

A

• Normal male fertility is dependent on normal spermatogenesis, erectile function and ejaculation.

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23
Q

Where does spermatogenesis take place? How? When?

A

• Spermatogenesis takes place in seminiferous tubules
o Undifferentiated diploid germ cells (spermatogonia) multiply and transformed into haploid spermatozoa
o Takes 74 days
o LH stimulates Leydig cells to produce testosterone
o Testosterone and FSH stimulate Sertoli cells to produce substances for metabolic support of germ cells and spermatogenesis

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24
Q

Causes of male infertility?

A
  • General Health
  • Semen abnormality (85%)
  • Azoospermia (5%)
  • Immunological (5%)
  • Coital dysfunction (5%)
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25
Q

General causes of male infertility?

A

o Obesity impairs fertility
o Smoking
o Tight-fitting underwear affect semen quality
o Alcohol consumption
o Anabolic steroids, marijuana, opioids, cocaine

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26
Q

Semen abnormality causes of male infertility?

A
  • Idiopathic oligoasthenoteratozoospermia (OATS)
  • Testis cancer
  • Drugs (inc. alcohol, nicotine)
  • Genetic
  • Varicocele
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27
Q

Azoospermia causes of male infertility?

A 
	Idiopathhic hypogonadotrophic hypogonadism (HH)
	Kalmann's, Klinefelter's
	Pituitary adenoma
	Anabolic steroid abuse
	Cryptorchism
	Orchitis
	Chemo-radiotherapy
	Congential bilateral absence of the vas deferens (CBAVD)
	Vasectomy
	STIs
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28
Q

Immunological causes of male infertility?

A

 Antisperm antibodies
 Idiopathic
 Infection

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29
Q

Coital dysfunction causes of male infertility?

A

 Erectile dysfunction
 Ejaculation normal (hypospadias, phimosis, disability)
 Retrograde ejaculation (diabetes, bladder neck surgery, phenothiazines)
 Failure in ejaculation (MS, spinal cord/pelvic injury)

30
Q

Key history parts of male subfertility?

General, infertility, sexual, PMH, Drug

A 
•	General Health
o	Smoking (stop), alcohol (reduce), recreational drug use (avoid), BMI (aim for normal)

• Infertility History
o Age, duration of subfertility, coital frequency & problems, any previous pregnancies in either partner

• Sexual History
o Previous/current STI, erectile dysfunction

• PMH
o Any relevant medical or surgical history, FHx, CKD, DM, anorexia

• Drug history
(recreational, steroids, alcohol, nicotine, marijuana, opioids)

31
Q

Examination of male subfertility?

A
  • Record BP, BMI
  • Examine male secondary sex characteristics, gynaecomastia, hirtutism
  • Site, consistency and volume
  • Examine presence of varicocele, swelling, lymphadenopathy
32
Q

When to offer investigations in male subfertility?

A

Offer investigation after 1 year of trying regular, unprotected sex

33
Q

Investigations performed in male subfertility?

A

• Semen analysis (specimen produced by masturbation after 3 days abstinence from sex)

34
Q

What parameters and normal values are there in semen analysis?

A 
o	Volume >1.5ml
o	Concentration >15 x106/mL
o	Total Motility >40%
o	Normal Forms >4%
•	Azoospermia = no sperm in ejaculate.
•	Oligozoospermia= reduced number of sperm in ejaculate (<15mil)
•	Asthenozoospermia (<32% motile spermatozoa)
•	Teratozoospermia (<4% normal forms)
35
Q

When to repeat semen analysis?

A

 Repeat abnormal test after 3 months

 If two tests abnormal – further testing

36
Q

What further investigations can be considered if abnormal male semen analysis?

A

o Screen for chlamydia
 Hormone analysis
• FSH and testosterone (FSH increased in testicular failure)
 Genetic testing (Karyotyping, exclude 47XXY)
 Testicular biopsy
 Cystic Fibrosis screen (CBAVD)

37
Q

General management of male subfertility?

A

Treat any underlying medical conditions
Address lifestyle issues ( alcohol, stop smoking)
Review medications
• Antispermatogenic (alcohol, anabolic steroids, sulfasalazine)
• Antiandrogenic (cimetidine, spironolactone)
• Erectile/ejaculatory dysfunction (α or β blockers, antidepressents, diuretics, metoclopramide)

38
Q

Medical management of male subfertility?

A
  • Gonadotrophins in hypogonadotrophic hypogonadism

* Sympathomimetics (e.g. imipramine) in retrograde ejaculation

39
Q

Surgical management of male subfertility?

A
  • Relieve obstruction
  • Vasectomy reversal
  • Surgical treatment of varicocele does not improve pregnancy rate and is therefore not indicated.
40
Q

Sperm retrieval techniques in male subfertility?

A
  • From postorgasmic urine in retrograde ejaculation

* Surgical sperm retrieval from testis with 50% chance of obtaining sperm (greater is FSH is normal)

41
Q

What assisted reproductive techniques can be used in male subfertility?

A

If sperm in ejaculate - ICSI and IVF

If no sperm in ejaculate - surgical sperm retrieval or donor sperm then IVF

42
Q

General management of infertility?

A 
Support and reassure
Support groups and counselling may help
Advice:
	Folic Acid supplements
	Regular 2-3 day sexual intercourse
	Reduce alcohol intake
	Stop smoking
	Optimise BMI
43
Q

Treatment of hyperprolactinaemia in female infertility?

A

• Dopamine agonists (bromocriptine)

44
Q

Define ART?

A

o Fertility treatments in which sperm and oocytes are handled with the aim of achieving pregnancy

45
Q

Define IUI? When is it considered?

A

With partner or donor sperm (in natural or stimulated cycles)
Introduction of prepared (partner/donor) sperm into uterine cavity around ovulation
Considered when:
 Difficulty having vaginal intercourse due to physical ailment or psychosexual problems
 After sperm washing where the man is HIV-positive
 Same-sex relationship

46
Q

What is IVF? Indication?

A 
o	In Vitro Fertilisation and Embryo Transfer (IVF-ET, widely known as IVF)
	Indications may include:
•	Tubal disease
•	Male factor subfertility
•	Endometriosis
•	Anovulation
•	Women <40 should be offered 3 cycles
•	Women >40 offered 1 cycle if:
o	Never had IVF, no evidence of low ovarian reserve, discussed implications for IVF and pregnancy at this age
47
Q

Success of IVF dependent on what?

A

Duration of subfertility
Age - 25-35
High AMH and FSH
Previous pregnancy

Reduced chance in smoking and high BMI.

48
Q

What is the method of IVF?

A
  • Ovarian stimulation with high dose gonadotrophins - multifollicular recruitment
  • Prevent premature LH surge using GnRH analogues (agonists OR antagonists, depending on cycle)
  • Follicles monitored by transvaginal USS
  • Trigger final oocyte maturation - hCG, GnRH agonist
  • Transvaginal oocyte retrieval by US guided needle aspiration (36 hours later)
  • Sperm sample collected (or thawed if frozen), prepared and cultured with oocytes overnight.
  • Fertilization checks of embryos
  • Embryo transfer by a fine catheter through cervix on day 2-3 (cleavage stage)
  • A maximum of two embryos are US transferred in women under 40.
  • Pregnancy test 2 weeks later
49
Q

What is pre-implantation genetic diagnosis?

A
  • Aims to reduce the recurrence of genetic risk in couples known to carry a heritable genetic condition.
  • Many couples are fertile, but IVF allows embryo biopsy, single cell diagnosis and the transfer of unaffected embryos to the woman.
  • Biopsies are usually done at cleavage stage and PCR or fluorescent in-situ hybridisation (FISH) used for genetic diagnosis.
50
Q

Define ICSI?

A

 A single sperm is injected into the ooplasm of the oocyte - then IVF
 Used for men with severely defects in sperm quality, obstructive/non-obstructive azoospermia and failed IVF treatment

51
Q

What is donor insemination?

A

Azoospermia, deficits in semen quality which don’t want ICSI, high risk of transmitting genetic/infectious disorder, Rhesus isoimmunisation]

52
Q

What is oocyte donation? Indicated when?

A

 May offer a chance of pregnancy for women previously considered to be irreversibly sterile
 Indicated in:
• Premature ovarian failure, Turners syndrome, bilateral oophorectomy, following chemo/radiotherapy, IVF failure
• Older women >45
 Risk of: preterm birth, low birth weight

53
Q

What is IVF surrogacy? Method?

A

 IVF surrogacy
 The couple who want the child provide both sets of gametes
 Following IVF the embryos are transferred to the surrogate
 Indications include women who have congenital absence of the uterus (Rotinkansky;s syndrome), following hysterectomy, or with severe medical conditions incompatible with pregnancy.

54
Q

What is natural surrogacy?

A

 The surrogate is inseminated by the sperm of the male partner of the couple wanting the child

55
Q

Other options for ART?

A

Adoption and fostering

56
Q

Complications of ART?

A

o Multiple pregnancies
o Higher risk of preterm birth
o Ovarian Hyperstimulation syndrome

57
Q

Cause of OHS?

A

 Systemic disease and VEGF cause pathology

• Causes capillary permeability and fluid shifts into third space compartments

58
Q

risk factors for OHS?

A
  • PCOS
  • Age <30
  • Use of hCG for luteal phase support
59
Q

Symptoms of OHS?

A
  • Symptoms start 24h after hCG administration but severe in 7-10 days
  • Ovarian enlargement
  • Ascites
  • Nausea and vomiting
  • Pleural effusions
  • Hypercoagulability
60
Q

Management of mild OHS?

A

o Outpatient – analgesia (AVOID paracetamol), restrict fluids, avoid strenuous activity and intercourse, avoid hCG
o Review by assisted conception unit every 2-3 days

61
Q

Management of severe OHS?

A 
o	Admit
o	Analgesia and antiemetics
o	Daily U&amp;E, LFT, FBC, albumin
o	Strict fluid balance
o	VTE prophylaxis
o	Paracentesis
o	May need ITU
62
Q

Fertility preservation in females?

A

GnRH analogues for ovarian suppression
Oocyte cryopreservation
Social egg freezing

63
Q

Fertility preservation in men?

A

Advisable before chemo, radio, surgery on testicle or reproductive tract

Sperm cryopreservation - in post-pubertal boys

64
Q

Management of premature ovarian insufficiency?

A

Oocyte donation

HRT

65
Q

Define Group 1 female infertility causes?

A

Hypothalamic pituitary failure (hypothalamic amenorrhoea, hypogonadotrophic hypogonadism)

66
Q

Define Group 2 female infertility causes?

A

HPO dysfunction (PCOS)

67
Q

Define Group 3 female infertility causes?

A

Premature ovarian failure (loss of ovarian activity <40)

Criteria: oligo/amenorrhoea >4 months and elevated FSH

68
Q

FSH and estrogen levels in group 1, 2 and 3 female subfertility causes?

A

Group 1 - Low/Normal FSH, Low Estrogen
Group 2 - Normal FSH, Normal Oestrogen
Group 3 - High FSH, Low Estrogen

69
Q

Define azoospermia?

A

Absence of sperm

70
Q

Define oligozoospermia?

A

Low sperm count

71
Q

Define asthenozoospermia?

A

Poor sperm motility

72
Q

Define teratozoospermia?

A

Morphological defects to sperm

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