FOLLICULOMETRY IN INFERTILITY
- Ovulation was initially monitored by conventional methods like BBT, mid luteal serum progesterone and urinary LH.
- Nowadays, USG is used for follicular monitoring for both natural and stimulated cycles.
- Vital component of IVF/IUI assessment and timing
- Employs a simple technique of assessing ovarian follicles on regular intervals, and documenting the pathway of ovulation.
- DAY 3 0R 4 SCAN-Baseline scan
- SERIAL FOLLICULAR MONITORING
WHY TO MONITOR:
- To evaluate if the dose being used is optimal
- To adjust the dose of the drug as some
- patients are hyperresponsive and some are
- poor responders
- To find optimal time for ovulation induction
- To time IUI
- To avoid exessive stimulation and prevent OHSS and multiple pregnancy
HOW TO MONITOR?
- By ultrasound, color doppler, power Doppler morphological growth of follicles
- By estradiol alone- indicates functional activity of follicles
- By both
- TVS –accepted method at all infertility clinics
Journey to ovulation begins during late luteal phase of prior menstrual cycle, when certain 2-5 mm sized healthy follicles form a population from which dominant follicles is to be selected for next cycle This process is called ‘recruitment’.
Usual number of such follicles may be 3-11, which goes on decreasing with advancing age. During Day 1-5 of the menstrual cycle, a second process of ‘follicular selection’ begins, when among all recruited follicles, certain growing follicles of size 5-10 mm are selected,while rest of the follicles regress or become atretic.
During Day 5-7 of the menstrual cycle, a process of ‘dominance’ begins, when a certain follicle of 10 mm size takes the control and becomes dominant. This also suppresses the growth of the rest of the selected follicles, and in a way, is destined to ovulate. This follicle starts growing at rate of 2-3 mm day and reaches 17-27 mm size just prior to ovulation.
One important learning point in this regard is, “largest follicle on day 3 of the cycle, may or may not be a dominant follicle in the end.
Process of dominance begins late, when suddenly a certain underdog follicle starts growing faster and suppresses others to become dominant”.
Almost nearing ovulation, rapid follicle growth takes place, and follicle starts protruding from the ovarian cortex, attains a crenated border, and it literally explodes to release the ovum, along with some antral
Ultrasound monitoring in induced cycles and predicting success of IVF
Most of the IVF studies are conducted after induction of ovaries with help of ovulation inducing agents like Clomiphene citrate. In
such induced cycle, primary determinants of success are:
- ovarian volume
- antral follicle number
- ovarian stromal blood flow
- is easy to measure,
- although not a good predictor of IVF outcome.
- a low ovarian volume does not always lead to anovulatory cycle.
- But, it’s important to recognize a polycystic ovarian pattern and differentiate it from post-induction multicystic ovaries.
- Follicles arranged in the periphery forming a ‘necklace sign’, echogenic stroma, and more than 20 follicles of less than 9 mm size, signify a polycystic pattern in induced cycle.
- While, follicles in the center as well as the periphery, are seen in normal induced multicystic ovaries.
Antral follicle number
Antral follicle number of less than three, usually signify possible failure of assisted reproductive therapy (ART).
Ovarian stromal blood flow
has been recommended as a good predictor of ART success. Increased peak systolic velocity (>10 cm/sec) is one of such parameters which has been advocated.
When to administer gonadotropins?
- Although, its a matter of choice, based on experience of individual IVF specialists, there are certain parameters which may be considered.
- Minimal criteria suggested is a follicle size of atleast 15 mm, and serum estradiol level of 0.49nmol/L.
- Better prospects are at follicle size of 18 mm, and serum estradiol level of 0.91 nmol/L.
- Random hCG administration should be avoided3, to prevent a risk of ovarian hyperstimulation syndrome (OHSS).
- Helps in prediction of impending ovulation and optimal timing for:
- Procedures like post coital testing,
- hCG administration,
- Intercourse, donor or husband insemination
- egg collection
- If not ovulating can be treated with ovulation induction agents.
- Diagnostic ultrasound can provide information that approximates a surgical assessment of reproductive anatomy without the expense and risks of a surgical procedure.
- Ultrasound can also be utilized repetitively throughout a single ovulatory cycle,
- providing dynamic information regarding ovarian function in a safe, convenient, noninvasive
- when properly applied, cost-effective manner
Importance of D-3/4 scan
- Antral follicle count
- To rule out any cyst.( > 3 cm)
- Endometrial shedding
- Or any other pelvic pathology
- We expect normal sized ovaries with very small follicles
(3—5 mm in diameter)
- Follicular size is measured by taking mean of 2 or 3 largest perpendicular diameters of each follicle .
Ultrasound follicular monitoring
Serial USG follicular monitoring is started from day 7 or 8 of the cycle
But in case of gonadotrophins we start scanning from 6th day of stimulation.
Assessing the follicular maturity
- The follicles normally grow at a rate of 2- 3 mm / day in a stimulated cycle.
- Definitive size of the follicle which confirms the maturity of oocytes is still controversial.
- A follicle measuring 18—20 mm has been found to contain a mature oocyte.
Corelation with serum oestradiol levels
- Plasma estradiol levels correlates closely with the stage of development of the dominant follicle
- Serum estradiol levels >200 pg / ml on day 8 of stimulation indicates adequate dose of gonadotropins.
- Ultrasound monitoring has totally replaced estradiol monitoring in most centers.
Predicting the risk of OHSS
- If there are more than 4 follicles larger than 16 mm or more than 8 follicles larger than 12 mm.
- It is best not to give hCG so as to prevent OHSS and
- high order multiple births.
- In case of doubt do serum estradiol levels
- Estradiol levels of > 1500 – 2000 pg/ml indicates risk of OHSS and is advisable to withhold hCG trigge
- Is a complication of ovarian stimulation treatment for IVF.
- Rarely, may occur as a spontaneous event in pregnancy
OHSS syndrome consists of:
- Weight gain
- Increase in abdominal circumference
- Pleural effusion
- Intravascular volume depletion with hemoconcentration
USG findings in OHSS:
- Bilateral symmetrical enlargement of ovaries(>12 cm in size)
- Multiple cysts of varying sizes- classic spoke wheel appearance
- Ascites and pleural / pericardial effusion may be present
Role of radiologist
- Familiarity with OHSS helps in avoiding the incorrect diagnosis of ovarian cystic neoplasm
- Appropriate management can be timely done
- OHSS has a significant risk for miscarriage in early phase after IVF(< 10 days after oocyte retrieval)
Treatment and prognosis:
- Self limiting
- Supportive mangement
- Some cases show fatal outcome
- Severe cases need hospitalisation
- Close monitoring of hematocrit, liver and renal function , serum electrolytes and O2 saturation
Follicular doppler flow studies
- A mature follicle shows vascularity in atleast ¾th of the follicular circumference and
- PSV is 10 cm/sec.
- At this time LH surge starts and
- This is the right time to give hCG trigger
Grade 1 : < 10%
Grade 2 : 10-25%
Grade 3 : 25-50%
Grade 4 : > 50%
Predictors of poor ovarian response are :
- Ovarian volume <3 cc
- < 3 antral follicles
- Ovarian RI > 0.6
- Ovarian PSV < 5 cm / sec
- Stromal flow index < 11
- Suggest poor ovarian response &
- Higher doses of gonadotropins will be required for stimulation.
- The end point of any ovulation induction
- protocol is to indentify the best time for
- triggering ovulation.
- In a gonadotrophin In clomiphene
Leading follicle is Leading follicle is
18 – 20 mm in diameter. 20 – 22 mm in size
Suggestive of ovulation:
- Disappearance of the follicle
- Presence of free fluid in the cul-de-sac.
- Presence of hyperechoic , smooth secretary endometrium.
Baseline, prior to initiating gonadotropin stimulation. Ovary with antral follicles
Stimulation day 5, showing recruited follicles measuring 10–12 mm
Stimulation day 7, showing ovary with leading follicle >12 mm
Stimulation day 9, showing ovary with growing follicles
Stimulation day 11, 2–3 follicles measuring 17–18 mm
Day of ovulation induction. Leading follicles measuring more than 18 mm
Five Reasons To Monitor
- To evaluate if the dose being used is optimal
- To adjust the dose of the drug as some patients are hyper responsive and some are poor responders.
- To find the optimal time for inducing ovulation
- To time IUI
- To avoid excessive stimulation , to prevent OHSS and multiple pregnancy
- “ In the hands of experienced operators , ultrasound and ultrasound alone suffices for cycle monitoring .”
- Need of extensive hormonal monitoring is no longer needed.