Follicular monitoring or follicular study is a vital component of in-vitro fertilization (IVF) assessment and timing. It basically employs a simple technique for assessing ovarian follicles at regular intervals and documenting the pathway to ovulation.
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 1.
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 a day and reaches 17-27 mm size just prior to ovulation 2. 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 fluid.
Ultrasound monitoring: general
Transvaginal ultrasound is preferred and usually mandatory modality for monitoring follicles. Ultrasound monitoring may begin on day 3 of the cycle, to assess a baseline size, as well as exclude if any cyst remains from previous hyperstimulation or otherwise. Its important to count the number of existing follicles, document two/three dimensions of each follicles, and also comment on shape (round/oval/rectangular/triangular), echogenicity (echogenic/hypoechoic/anechoic) and antral edges (smooth/intermediate/rough) if possible.
As the study progresses on day 7, we should start guessing the ovulatory dominant follicle i.e. dominant follicle which is destined to ovulate. Basically, there are three varieties of eligible follicles:
- atretic dominant follicle: This follicle is usually largest follicle on day 3, but it is not destined to ovulate. It has an irregular shape, rough edges, and may be little echogenic.
- ovulatory dominant follicle: This follicle is typically round, with smooth borders, and usually hypoechoic.
- anovulatory-luteinizing dominant follicle: This dominant follicle grows at a good pace but fails to ovulate, and later becomes a cyst or luteinizes. These are also round and smooth, however anechoic. This subtle recognition of echogenicity difference between hypoechoic and anechoic follicle can help determine whether a follicle is growing to ovulate.
Once the follicle reaches 16 mm size, a daily monitoring of follicle is recommended.
Next step is documentation of ovulation. Ovulation is sonographically determined by the following sonographic signs:
- follicle suddenly disappears or regresses in size
- irregular margins
- intra-follicular echoes. Follicle suddenly becomes more echogenic
- free fluid in the pouch of Douglas
- increased perifollicular blood flow velocities, on doppler
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
Ovarian volume is easy to measure, although not a good predictor of IVF outcome. Now, it is documented, that a low ovarian volume does not always lead to anovulatory cycle. But, it is 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 10 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 4.
Antral follicle number of less than three 5, 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, it is a matter of choice, based on experience of individual IVF specialists, there are certain parameters which may be considered. Minimal criteria 6 suggested is a follicle size of at least 15 mm, and serum estradiol level of 0.49 nmol/L. Better prospects are at follicle size of 18 mm, and serum estradiol level of 0.91 nmol/L.
Random hCG administration should be avoided 3, to prevent a risk of ovarian hyperstimulation syndrome (OHSS).
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- 2. Bakos O, Lundkvist O, Wide L et-al. Ultrasonographical and hormonal description of the normal ovulatory menstrual cycle. Acta Obstet Gynecol Scand. 1994;73 (10): 790-6. - Pubmed citation
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- 4. Adams J, Franks S, Polson DW et-al. Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet. 2 (8469-70): 1375-9. - Pubmed citation
- 5. Chang MY, Chiang CH, Hsieh TT et-al. Use of the antral follicle count to predict the outcome of assisted reproductive technologies. Fertil. Steril. 1998;69 (3): 505-10. Fertil. Steril. (link) - Pubmed citation
- 6. Vlaisavljević V, Kovacic B, Reljic M et-al. Three protocols for monitoring follicle development in 587 unstimulated cycles of in vitro fertilization and intracytoplasmic sperm injection. A comparison. J Reprod Med. 2001;46 (10): 892-8. - Pubmed citation