Excessive ovarian response during in-vitro fertilisation treatment

by Ng, Hung-yu

(Uncorrected OCR) Abstract of the thesis entitled

"EXCESSIVE OVARIAN RESPONSE DURING IN-VITRO FERTILISATION TREATMENT"

Submitted by Dr. Ernest Hung Yu NG

For the degree of Doctor of Medicine

at the University of Hong Kong in February 2004

Ovarian stimulation is being routinely used during in-vitro fertilisation and

embryo transfer (IVF / ET) treatment to improve the success. However, excessive ovarian

responses may impair the outcomes. A retrospective analysis of 1122 patients of age <40

years undergoing their first IVF cycle demonstrated that pregnancy rate (PR) was

significantly lower in patients with serum oestradiol (E2) concentrations on the day of

HCG >20,000 pmol/L (excessive responders) than those with E2 10,000-20,000 pmol/L,

despite similar number of embryos replaced. Implantation rate (IR) was also much

reduced in excessive responders. The corresponding PR and IR were comparable in

subsequent frozen thawed embryo transfer cycles, regardless of serum E2 in the

stimulated cycle. Another retrospective study of 278 patients in their intracytoplasmic

sperm injection cycle for severe male factors further supported that oocyte / embryo

quality was not compromised in excessive responders. These data strongly suggested that

reduced IR and PR in cycles with high E2 concentrations were related to an adverse

endometrial environment.

A rapid decline in E2 concentrations around the mid-luteal period could not

explain the impaired endometrial receptivity associated with excessive response as shown

by similar PR of excessive responders with different E2 ratio. A previous study from this

Department showed delayed glandular maturation and advanced stromal morphology in

excessive responders but synchronous development of glandular and stromal features in

moderate responders i.e. E2 ::;;20,000 pmol/L.

Utero-ovarian vessels and endometrial colour signals were assessed by colour

Doppler ultrasound in 58 patients on the day of ET. Doppler flow indices were

significantly lower In exceSSIve responders but the number of women showing

endometrial colour signals was significantly lower In exceSSIve responders.

Three-dimensional (3D) power Doppler ultrasound examination was performed in

another 32 patients who did not have ET during the early luteal phase to objectively

measure endometrial and subendometrial blood flow. Excessive responders tended to

have lower endometrial / subendometrial3D power Doppler flow indices on HCG +2 and

were more likely to have absent endometrial / subendometrial blood flow. A decline of

uterine Doppler flow indices during the early luteal phase but an increase in endometrial

3D power Doppler flow indices by HCG +7 were found in excessive responders only.

Uterine flushings were performed in 107 patients during natural and stimulated

cycles to examine the secretory functions of the peri-implantation endometrium.

ii

Concentrations of the total protein, PP 14 and CA-125 in uterine flushings were similar

among patients in natural cycles, moderate and excessive responders. These data

indicated that there were no significant difference between natural and stimulated cycles

in concentrations of PP 14 and CA-125 in uterine flushings performed in the mid-luteal

phase.

A study of 128 consecutive patients using a standard stimulation regimen in the

first IVF cycle demonstrated that antral follicle count achieved the best value, followed

by basal FSH, body mass index and age of women in predicting the number of oocytes

obtained after stimulation. This information is useful in tailoring the individual dosage to

prevent excessive response in those who are prone to it.

(Words: 499)

Keywords: antral follicle count, oestradiol level, endometrial blood flow, endometrial

proteins, excessive response, oocyte quality, pregnancy rate

iii