1. Practical tips for monitoring of an IUI cycle Dr. Jyoti Agarwal

2. Introduction Ovulation induction though sounds simple but there are many obstacles, as each patient behaves in a different fashion. Variety of drugs and protocols are available. Every center has its own pattern of COH but the basic concept of monitoring remains the same.

3. Who should monitor? Do it yourself Why add to the burden ?

4. “Vision is the art of seeing invisible ” Jonathan swift It is difficult to think of managing an infertile couple without resorting to this versatile and easy to use technology. All the modalities of ultrasound ranging from basic black and white to the most complex, real time 3 – D and colour doppler have a role to play in managing these infertile patients.

5. 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 All patients to be monitored

6. Monitoring Should Be Easy Reliable Patient friendly Not expensive Can be done by self

7. How to monitor ? BY E 2 ALONE BY ULTRASOUND ALONE BY BOTH BY COLOR POWER DOPPLER BY OTHER HORMONES MINIMUM MONITORING

8. Monitoring Ultrasound states the morphological growth of the follicles Hormones indicates the functional activity of the follicles TVS is the accepted method by all ART centers.

9. Why TVS ? Simple Easy Reproducible Reliable Cheap Can be done repeatedly Patient friendly Antral count/ovarian volume /color doppler/ 3 D An transvaginal probe is an extension of clinician’s fingers

10. Importance of D -2 scan TVS is performed on day 2 of the cycle to see for 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) Follicles are of clinical importance only when their size is 10 mm Follicular size is measured by taking mean of 2 or 3 largest perpendicular diameters of each follicle.

11. 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 6 th day of stimulation.

12. Assessing the follicular maturity T he 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.

13. 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.

14. 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 trigger.

15. Follicular doppler flow studies A mature follicle shows vascularity in atleast ¾ th of the follicular circumference & PSV is 10 cm/sec. At this time LH surge starts and This is the right time to give hCG trigger

16. Interpretation of ovarian indices Rising PSV & steady low RI suggests follicle is close to rupture Decreasing PSV & rising RI suggests follicle is likely to become LUF. Fertilisation of a follicle with PSV of less than 10 cm /sec may result in an embryo with chromosomal abnormality.

17. Perifollicular vascularisation Grade 1 : < 10%Grade 2 : 10-25% Grade 3 : 25-50%Grade 4 : > 50%

18. 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.

19. ENDOMETRIAL EVALUATION Clear association between endometrial growth and the circulating estrogen & progesterone levels.

20. Endocrine implantation ET – 8 – 14 mm BEST ENDOMETRIUM ON THE DAY OF HCG TRIGGER ET > 16 mm or < 7mm Is not associated with good prognosis

21. Proliferative phase : 4- 7 mm Periovulatory period : 6-10 mm Secretory phase : 8-12 mm Postmenopausal pd. : < 4 mm Thickest part of the endometrium should be measured

22. D-2 Can show  anechoic collection of blood.  thick echogenic endometrial echo.  a very thin endometrium 1-3 mm thick.

23. D3-7 Increase in oestrogenic biosynthesis leads to stimulation and growth of endometrial glands and stroma. Double line endometrium is seen which is usually < 6 mm.

24. D-7 onwards Proliferative endometrium continues to grow in size and thickens and is seen as a triple layer or triple line. Middle layer echogenic—Lumen Hypoechoic area surrounding the lumen—Endometrium functionalism Hyperechoic ring outside— Endometrium basalis

25. In Periovulatory Phase characteristic changes start only 24 hrs post ovulation. Triple line progressively becomes thicker, homogenous and hyperechoic

27. Applebaum’s uterine scoring system for reproduction (USSR)

28. Cyclical Endometrial Changes Power Doppler evaluation

29. Endometrial evaluation Conception rates according to zones of vascularity Zone 1 5.2 % Zone 2 28 % Zone 3 52 % Zone 4 74%

30. COLOR DOPPLER UT.ARTERY DAY 2

31. DAY 7-9

32. PERIOVULATORY UT A.

33. Uterine Artery Doppler The chance for pregnancy is almost zero if the PI is more than 3.019 on the day of hCG administration Patients who get pregnant have a lower RI (0.53 vs 0.64)

34. Doppler study for uterine receptivity Uterine artery RI 0.60 – 0.80 PI 2.22 –3.16 No pregnancy if VI < 1.0, FI < 31 and VFI < 0.25 Smoking is associated with significantly lower VI and VFI.

35. Subendometrial Vascularisation Presence of subendometrial flow is an indicator of good endometrial receptivity If pregnancy occurs in patients with absent subendometrial flow more than half of these pregnancies will result in abortion

36. 3 D power doppler for endometrial receptivity Endometrial volume is a more reliable parameter than endometrial thickness Favourable endometrial volume is 4.28 – 1.9 ml. No pregnancy occurred if endometrial volume is <1 ml. 3D tells us also about global vascularity of the endometrium

37. Cervix and follicular monitoring On D – 13 scan Good cervical mucus E2 > 100 pg 2 follicles ET 7-8 mm

38. Application of 3 D us for follicular assessment Cumulus may be seen in almost 90 % of the follicles using 3 D usg rendering. Where as it is seen only in 25 % of follicles by 2D usg. On the day of hCG if cumulus is not seen in all the three planes by 3D usg, it is less likely to be mature follicle. Infolding of inner cell mass of granulosa layers

39. hCG timing ALWAYS TIME HCG WITH FOLLICLE SIZE

40. Ovulation trigger The end point of any ovulation induction protocol is to indentify the best time for triggering ovulation. most crucial step In a gonadotrophin In clomiphene Leading follicle is Leading follicle is 18 – 20 mm in diameter. 20 – 22 mm in size

41. Ovulation to be confirmed by Disappearance of the follicle Presence of free fluid in the cul-de-sac. Presence of hyperechoic, smooth secretary endometrium.

42. Timing of insemination IUI is done 24 hrs. after LH surge is detected IUI is done 36 - 38 hrs. after hCG injection

43. serum progesterone and implantation Periovulatory progesterone levels are used as a predictor of outcome. Elevated levels of serum progesterone in the late follicular phase is associated with diminshed chances of conception.

44. Premature LH surge Premature LH surge is known to occur in approx 15-25 % of patients once the leading follicle is 16 mm. Urinary LH kits are available to detect LH surge. A blood level of >10 IU /L correlates with the LH surge

45. Premature LH surge If an LH surge is detected, injection hCG is given immediately. The hCG injection is required to supplement the LH secreted by the body as it is not adequate enough to induce the final maturational changes in all the follicles. IUI is done 24 hrs after the LH surge

46. Luteal phase scan A healthy corpus luteum shows a good vascular ring on colour doppler RI of 0.35 – 0.50 PI of 0.70 – 0.80 PSV of 10 – 15 cm / sec. RI of corpus luteum corelates well with plasma progesterone level which is an index of luteal function.

47. To conclude “ In the hands of experienced operators, ultrasound and ultrasound alone suffices for cycle monitoring, with no necessity for additional hormonal estimations.” NEED OF EXTENSIVE HORMONAL MONITORING IS NO LONGER NEEDED

48. All The Best to all of you to design your own Minimal Monitoring Protocol THANK YOU FOR HEARING ME OUT