QuestionSBA
QuestionChoice
Pituitary apoplexy is bleeding or infarction of the pituitary, usually in the context of a pre-existing pituitary adenoma or in postpartum haemorrhage. This would lead to a fall in the pituitary hormones LH and FSH and subsequently low levels of oestrogen. In this case, there is no history consistent with pituitary apoplexy, such as a sudden-onset headache, and the levels of FSH and LH are high, indicating primary ovarian failure.
53065
d
Pituitary apoplexy
QuestionChoice
Primary ovarian failure results in a reduction of ovarian oestrogen production. The drop in oestrogen reduces negative feedback on the pituitary gland, which produces more LH and FSH in response. Her AMH is also low; this is a measure of the number of eggs that the patient has remaining, further pointing towards ovarian failure.
53062
a
Primary ovarian failure
QuestionChoice
Hypothyroidism can cause amenorrhoea and infertility in females. It causes a hypogonadotrophic hypogonadism as raised thyrotropin-releasing hormone levels stimulate prolactin release, which suppresses gonadotropin-releasing hormone release. In this patient, the LH/FSH are raised, making this less likely. This patient also lacks other features of hypothyroidism, such as weight gain, hair loss and cold intolerance.
53066
e
Hypothyroidism
QuestionChoice
During pregnancy, LH and FSH levels are low due to negative feedback from higher levels of oestrogen. This patient has low oestrogen levels alongside low FSH and LH. This indicates ovarian failure rather than pregnancy. They do not report any symptoms in keeping with pregnancy either, such as morning sickness, weight gain or breast tenderness. However, in practice a pregnancy test would be conducted to definitively rule this out in any patient presenting with secondary amenorrhea.
53063
b
Current pregnancy
QuestionChoice
Hypothalamic hypogonadism would result in low levels of LH, FSH and subsequently oestrogen, due to lack of gonadotropin-releasing hormone release stimulating the pituitary gland. This usually occurs in the context of anorexia or excess exercise. The patient in this case has a normal body mass index and there is no mention of excessive exercise.
53064
c
Hypothalamic hypogonadism
QuestionComment
Why is the Prolactin high? As well as the TSH?

53595
User
subscriber
Supine Bladder
Concept
Chapter
# Summary
  
 
Subfertility is defined as the diminished ability of a couple to conceive a child, which may be due to a variety of definable causes or an unexplained failure to conceive over a two-year period. Key signs and symptoms vary based on the underlying cause but generally revolve around the inability to achieve pregnancy despite regular unprotected sexual intercourse. Investigations typically include hormonal studies, semen analysis, and imaging studies. The management of infertility is dependent on the underlying cause and often involves a combination of lifestyle modifications, medical interventions, and assistive reproductive technology. 
  
   
 
# Definition
  
Infertility is the diminished ability of a couple to conceive a child. This may result from a definable cause such as ovulatory, tubal, or sperm problems, or may be an unexplained failure to conceive over a two-year period despite regular (3-4 times a week) unprotected sexual intercourse.
  
 
  
# Epidemiology
  
 
Statistically, a couple stands an 80% chance of conceiving within one year if the woman is younger than 40 years, they do not use contraception, and they have regular intercourse (3-4 times per week). This overall probability increases to 90% if considered over two years.
  
 
# Aetiology

 
Factors affecting natural fertility include:
 
  - Increasing age
  - Obesity
  - Smoking
  - Tight-fitting underwear (males)
  - Excessive alcohol consumption
  - Anabolic steroid use
  - Illicit drug use
  
 

Causes of infertility can be classified into:
  
 
  - **Genetic causes:** This includes Turner's syndrome (XO) and Kleinfelter's syndrome (XXY).
  - **Ovulation/endocrine disorders:** Examples are polycystic ovary syndrome, pituitary tumours, Sheehan's syndrome, hyperprolactinaemia, Cushing's syndrome, and premature ovarian failure.
  - **Tubal abnormalities:** These can be due to congenital anatomical abnormalities or adhesions secondary to pelvic inflammatory disease (often caused by chlamydia or gonorrhoea).
  - **Uterine abnormalities:** These include bicornate uterus, fibroids, and Asherman's syndrome (uterine adhesions).
  - Endometriosis
  - **Cervical abnormalities:** These include cervical damage after biopsy or LLETZ procedure.
  - **Testicular disorders:** Disorders such as cryptorchidism, varicocele, testicular cancer, and congenital testicular defects fall in this category.
  - **Ejaculatory disorders:** These include obstruction of the ejaculatory system and disorders of ejaculation such as retrograde ejaculation and premature ejaculation.
  
 
# Investigations
  
 
Investigations for infertility are divided into those for men and women. 

*For women:*

**Bedside:**
 
- Thorough history, including past medical history, sexual history and details of past pregnancies. 
- Speculum and bimanual examination: To investigate physical anomalies (e.g. large fibroids). 
- STI screen
 
 
**Bloods:**
 
  - Serum progesterone testing (performed 7 days before the end of the menstrual cycle): A rise in progesterone indicates that the corpus luteum has formed and is releasing progesterone due to occurrence of ovulation.
  - Prolactin
  - LH/FSH 
  - Anti-mullerian hormone (AMH): Measure of ovarian reserve
  - TFTs 

 
**Imaging:**
 
- Transvaginal ultrasound scan: To identify any physical anomalies of the uterus, and check antral follicle count (measure of ovarian reserve)
- Hysterosalpingography: Assess tubal patency.
- Laparsocopy and dye: Assess tubal patency in presence of co-morbidities (e.g. PID, ectopic pregnancy, endometriosis). 


*For men:*

**Bedside:**
 
- Thorough history, including past medical history, sexual history and details of past pregnancies. 
- Testicular examination: To investigate visible physical anomalies (e.g. varicocele). 
- Semen analysis: To evaluate sperm count, motility, and morphology. 
 
 
**Bloods:**
 
  - Serum testosterone 
  - LH/FSH 
  - TFTs 
  
 
# Management
  
 
The management of infertility is tailored to the underlying cause but may include:
  
**Conservative:**

  - Weight loss
  - Smoking cessation 
  - Reduction of alcohol intake
  - Stress-reduction strategies

**Medical:**

Medications may be used for ovulation induction, such as: 

  - Clomiphene
  - FSH and LH injections
  - GnRH or DA agonists

  
**Surgical:**
  
  - Assisted reproductive technology, including in vitro fertilisation or intracytoplasmic sperm injection.


In addition to all of the above, if an underlying cause of infertility is found (e.g. fibroids, endometriosis), then those causes should be managed. 


# NICE Guidelines

[Click here for NICE Guidelines on fertility problems](https://www.nice.org.uk/guidance/cg156)

[Click here for NICE Guidelines on infertility](https://cks.nice.org.uk/topics/infertility/)

# References 

[BMJ Best Practice](https://bestpractice.bmj.com/topics/en-gb/498)

[Fields et al., 2023 - BMJ](https://www.bmj.com/bmj/section-pdf/187753?path=/bmj/346/7896/Practice.full.pdf)
929
976
Subfertility
Topic
26
Gynaecology
Condition
423
Menopause
UkmlaTopic
18
Obstetrics and gynaecology
10673
Primary ovarian failure is characterised by elevated LH and FSH levels, low oestradiol, and decreased anti-Müllerian hormone, indicating reduced ovarian function.
Presentation
520
Subfertility
UkmlaTopic
18
Obstetrics and gynaecology
A 32-year-old woman presents to her GP concerned over her periods. She used to have regular 28-d cycles but over the past 2 years she has experienced these becoming irregular and then ceasing for the past 4 months. Her GP arranges for her to have some blood tests, which are shown below:

||||
|--------------|:-------:|---------------|
|Luteinising Hormone|12.2 IU/L|1 - 11 (Luteal)|
|Follicle Stimulating Hormone|42.3 IU/L|2 - 8 (Luteal)|
|Testosterone|1.1 nmol/L|(M) 9.9 - 27.8, (F) 0.2 - 2.9|
|Prolactin|520 IU/L|(M) 90 - 320, (F) 100 - 500|
|Thyroid Stimulating Hormone|4.5 mU/L|0.3 - 4.2|
|Oestradiol|22 pmol/L|45 - 854|
|Anti-Müllerian hormone (AMH)|2.2 pmol/L|6.8 - 47.8|


What is the most likely diagnosis?
a