Infertility: Female

Question 1

Definition of infertility/ subfertility

Answer 1

Inability of a couple to achieve a clinical pregnancy within 12 months of beginning regular unprotected sexual intercourse
=Around 84% of the normal fertile population will conceive within 1 year and 92% by the end of 2 years

Question 2

Definition of Fecundability

Answer 2

Probability of achieving a pregnancy in one menstrual cycle

=Percentage of women exposed to the chance of a pregnancy for one menstrual cycle who will subsequently produce a live-born infant (normal range 15% – 28%). Fecundability decreases with increasing age, and hence diminishes slightly with each passing month of not conceiving.

Question 3

Definition of Fecundity

Answer 3

-Probability of achieving a pregnancy resulting in a live birth in one menstrual cycle
-1 in 6 couple will experience a difficulty with conception in their reproductive lifetime

Question 4

What is needed for natural conception?

Answer 4

-Healthy individuals
-Sexual intercourse
-Sperm
-Oocyte
-Fallopian tubes
-Uterus
-Lifestyle & environmental issues

Question 5

Psychological stress in infertility

Answer 5

-Counselling
-Fertility support group
-Relationship problems, reduced libido

Question 6

Who gets referred to a specialist team?

Answer 6

-Female < 36 no known cause of subfertility:
=1y unprotected vaginal intercourse
=6 cycles of artificial insemination
-Female age 36+ or known cause of subfertility: Sooner

Question 7

Causes of subfertility

Answer 7

-27% ovulatory disorder
-25% Unexplained
-24% male factor (increasing)
-14% tubal disease
-5% endometriosis
-5% others

Question 8

Lifestyle and environmental factors of female infertility

Answer 8

-Obesity (BMI 30+)
=Ovulation, fecundity, miscarriage
-Low BMI (<19), especially if menstrual cycle issue

-Cigarette smoking
=Mucous, ciliary, E2 prod, increased oocyte diploidy, uterine receptiveness, embryo implantation
-IVF outcome

-Alcohol
=Embryo, foetus, ?fecundability

-Caffeine (>300-500mg/day)
=Prolong delay before conception

Question 9

Pre pregnancy advice

Answer 9

-Balanced diet (Rainbow fruit and Vegetable; Protein, Nuts)

-Alcohol
=No binge drinking
=0-2 units/week Women; < 14 unit /week Men

-No Tobacco/ Nicotine (No Vaping); No recreational drugs

-Limit caffeine to <= 200 mg/D

-Folic acid supplementation (Women)
=400 mcg/D BMI < 30
=5mg/D BMI 30+
-Vitamin D supplementation (10 mcg/D)
-Up to date cervical screening

Question 10

Questions for infertility history

Answer 10

-Duration of subfertility
-Age (female)
-Prior known/documented fertility
-Lifestyle
-Intercourse (timing, frequency, problems)
-History of STD/PID
-Current and past medical/ surgical illnesses
-Menstrual history (female)

Question 11

Female factors in subfertility

Answer 11

Oocyte production and quality
-WHO classification ovulation dysfunction
-Age-related declined in fertility (decrease in oocyte quantity and quality)
-Endometriosis/tumour

Tubal disorders
→Infectious :PID/chlamydia, tuberculosis, septic abortion ruptured appendix
→Non infectious :Endometriosis, pelvic surgery congenital anomalies, SIN, Sterilisation

Question 12

Examples of uterine diseases

Answer 12

Congenital:
-Mullerian duct anomalies
-In utero exposure to DES

Acquired:
-Fibroid
-Asherman syndrome
-Uterine infection
-Adenomyosis

Question 13

Ovulation investigations

Answer 13

-History (regular cycle)
-Urinary LH= identifies mid-cycle surge of LH
-Mid luteal phase progesterone >28nmolL
=Weekly E2 + Prog (Irreg cycle)
=USS cycle tracking
=BBT Chart/ LH Kit

-Early follicular phase: luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone (AMH)
-Rubella (offer vaccination if not immune)

Question 14

What are Ovarian reserve tests?

Answer 14

-Not routinely on regularly menstruating woman, especially if <38 y (no correlation with spontaneous conception rate).
-Indicated if irregular periods/ oligoamenorrhoea

=D2-5
=FSH/LH (FSH <10= age related level)
=AMH (ant-Mullerian hormone)
=AFC (USS, early follicular-phase antral follicle count)
=CCCT (clomifene citrate challenge test)

Question 15

Investigations of the reproductive tract

Answer 15

-Clinical examination
-Pelvic Ultrasound scan (2D/3D)= ovarian morphology and uterine abnormalities
-Tubal patency tests (After sperm test if applicable)
=Hysterosalpingogram/ HYCOSY for no risk factors
=Laparoscopy (and dye for risk factors, endometriosis)
=Hysteroscopy= intrauterine anomalies
=Salpignoscopy
=MRI
-Prolactin and thyroid function tests, testosterone to calculate Free Androgen Index (PCOS)

Question 16

Describe uterine malformations

Answer 16

-2 uterus, risk pre-term delivery
-Most don’t stop you get pregnant, but influences outcome
=Big septum can increase miscarriage risk

Question 17

Management of female subfertility

Answer 17

-Expectant management
=unilateral tubal occlusion with short duration subfertility

-Medical management: Ovulation induction
=Clomiphene citrate
=Aromatase inhibitor
=Gonadotrophin
=Consider side effects, multiple pregnancy, OHSS

-Surgical management
=Ovarian drilling
=Tubal surgery: no evidence of benefit
=Uterine surgery (Polyps, fibroid, synechiae, septum)
=Endometriosis: Laparoscopic surgical ablation (mild/moderate endometriosis)/ Laparoscopic cystectomy for endometriomas (But ovarian reserve impact)

-Assisted reproduction
1. Intrauterine insemination
=NICE suggests for minimal to mild endometriosis: controversial
2. IVF
=Age related success rate
=OHSS
=Other complications
=Multiple pregnancies
=Disparity in NHS FUNDING

Question 18

Management of unexplained causes of subfertility

Answer 18

-Expectant management
=Do not offer empirical ovulation induction
=Offer IVF at 2 years mark
=Evidence from other part of world benefit of IUI

-Fertility preservation
=Gametes
=Ovarian tissue
=Embryo
-PGD
-Surrogacy
-Adoption
-Life without a child

Question 19

Examination of female in subfertility

Answer 19

-Height and weight to calculate body mass index (BMI)= High or low BMI associated with lower fertility: change of weight of >10% in the preceding year may cause a disturbance of the menstrual pattern and anovulation. A BMI at either extreme is detrimental to fertility
-Body hair distribution= Hyperandrogenism (PCOS)
-Galactorrhoea in breast exam= Hyperprolactinaemia
-Uterine structural abnormalities (most usefully determined by transvaginal ultrasound)= May be associated with subfertility
-Immobile and/or tender uterus= Endometriosis or pelvic inflammatory disease
-Pelvic examination is important to look for signs of structural abnormalities, infection and pathological processes, such as endometriosis or pelvic inflammatory disease

Question 20

Causes of anovulation

Answer 20

-Ovarian failure is found in about 50% of women with primary amenorrhoea and 15% of those presenting with secondary amenorrhoea.
-Most women with primary amenorrhoea will have an established diagnosis before presenting to a subfertility clinic.
=The cause may be genetic, for example, Turner syndrome (45,XO), or autoimmune.
-In those presenting with secondary amenorrhoea and ovarian failure, there may be an obvious cause, such as previous ovarian surgery, abdominal radiotherapy or gonadotoxic chemotherapy. There will also be a proportion of women in whom no reason can be identified, termed ‘idiopathic premature ovarian insufficiency’ (POI).

=Weight-related (22% body weight minimum)- weight loss= disappearance of 24-hr secretory pattern of Gnrh= multifollicular appearance USS
-PCOS (50%)
-Luteinized unruptured follicle syndrome (oocyte retained following LH surge)
-Hyperprolactinaemia (galactorrhoea, bitemporal hemianopia)

Question 21

Women at risk of diminished ovarian reserve

Answer 21

(1) are over 35 years of age;
(2) have a family history of early menopause;
(3) have a single ovary or history of previous ovarian surgery, chemotherapy or pelvic radiation therapy;
(4) have unexplained subfertility;
(5) have demonstrated a poor response to gonadotropin stimulation; or
(6) are planning treatment with assisted reproductive technology (ART).

Question 22

Classification of tubal patency

Answer 22

-Distal: fimbrial end
=Agglutination of fimbria to produce narrowed opening (phimosis)
=Complete agglutination to form hydrosalpinx (fluid-filled tube)
-Proximal: cornu
-Peritubal adhesions
-Endosalpinx (with intraluminal adhesions and flattening of mucosal folds)

Question 23

Features for fertility prognosis in tubal patency

Answer 23

-Degree of dilatation of the fallopian tube
-Extent of fibrosis of the wall of the tube
-Damage to the endosalpinx
-Whether one or both tubes are affected

Question 24

Tests of tubal patency

Answer 24

-In the absence of a positive history suggestive of pelvic pathology,
-negative physical examination
-and negative Chlamydia test, the least invasive method for assessing tubal patency should be employed