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Abstract Endometrial adequacy is important in implantation. Accurate assessment of luteal adequacy is of critical importance in an investigation of the infertile couples. LPD is identified as a repetitive entity in about 10% of infertile women (Wentz, 1990). The test of luteal adequacy currently available however, are less than ideal. At present, the PEB is the diagnostic method of choice of LPD. A lag of 2 days or more in at least 2 cycles is necessary to support the diagnosis The present study was performed to evaluate the merit of ultrasonagraphic assessment of (A) follicular development & (B) endometrial changes throughout the menstrual cycle as a diagnostic tool for LPD. This methodology is comfortable and harmless and could be repeated in clinical practice. This study was conducted on two groups of women : Group (I) (Study group): _ Consists of 50 women with only LPD selected from the patients complaining of Iry infertility for at least IY. Group (II) : (Control group) : _ Consists of 50 normal healtly fertile women. The followingwere done for each women in both groups for two consecutive cycles: -188- .summar!! &: Conclusion 1- Serial ultrasonographic examination by abdominal sector probe 3.5MHz, starting from menstrual day 8 every other day or every day according to the size of the follicles till ovulation, then every two or three days till next menstruation, to assess the follicular development & endometrial characteristics (thickness, echogenicity & posterior acoustic enhancement). 2- PEB on PsOD 12 or 13 (12 or 13 days after expected ovulation in LUFs), for histologic dating ofthe endometrium 3- Mid-luteal serum progesterone level on PsOD 7 (7 days after expected ovulation in LUFs), using RIA technique. Analysis of the results revealed atbe following items: o Ultrasound assessment showed that: a- Follicular growth in cases ofLPD patients (study group) showed 3 different growth patterns. (I) cycles with normal size follicles (44%). (II) cycles with small size (immature) fellicles (51%).(III) cycles with LUFs (5%). THe patients could be seen with only one pattern, normal size follicles (44%), small size follicles (50%) & LUFs (4%), or with mixed pattern (2%) (one cycle with small size follicle & the other with LUFs). In normal women (control group), all the women showed normal size follicles. b- Endometrial echogenicity m LPD patients (study group) was different from that in the normal women (control grpup) . -189- Summary & Conclusion • In LPD cycles with normal follicles & LUFs, endometrial echogenicity was adequate in late follicular phase (Pattern I) & adequate in the mid-secretory phase (Pattern III), but it could not maintain this adequacy & regressed to the inadequate pattern (Pattern II) in the last four days preceding menstruation. • In LPD cycles with immature follicles, endometrial echogenicity was inadequate in late follicular phase (Hypoechoic pattern) & was inadequate in the mid secretory phase (Patten II). This inadequate pattern was persistent up to menstruation . • In normal women (control grpup), endometrial echogenicity in most women (92%) was adequate in late follicular phase (Pattern I), (5%) was inadequate (Hypoechoic pattern) & (3%) was advanced (Pattern III). The women with adequate late follicalar growth were also adequate in the mid secretary phase (Pattern III), (90%) of them maintined this adequacy up to the late secretory phase & only (2%) regressed to inadequate pattern (Pattern II). The women with inadequate late follicular growth, were also inadepuate in the mid secretory phase (Pattern II) & persisted with this inadequate pattern up to the late secretory phase. The women with advanced pattern in the late follicular phase (Pattern III), maintained this pattern up to the late secretory phase. * At day of ovulation (expected ovulation in LUFs), endometrial echogenicity could help in detection of only 51% ofLPD cycles (cycles with immature follicles) with the inadequate (Hypoechoic -190- c’3ummary ’” Conclusion pattern). The other 49% ofLPD cycles (cycles with normal follicles & LUFs) showed adequate (Pattern I). In normal women (control groups), 92% were with adequate (Pattern I) & 8% were non adequate (5% hypoechic & 3% advanced patterns). The sensitivity was 51%, the specificity was 92%, the positive predicitive value was 86.4%. & the negative predicitive value was 65.2%. The importance of study of the echogenicity at that time is to detect the maturity of the follicle whatever its size (through the adequacy of the pattern) and to foretell the adequacy in the mid-secretory phase (the time of nidation). Since all the patients with adequate late follicular growth will be seen with adequate mid-secretory growth & all the patients with inadequate growth will be seen with inadequate mid-secretory growth. • At the mid-secretory phase (psOD 7), endometrial echogenicity could not detect more than what was detected before at day of ovulation. Evaluation at that time is needed either to confirm the results at ovulation or when the patient is missed to follow at ovulation. The same group of LPD (cycles with immature follicles) 51%, showed the inadequate mid-secretory (pattern II), which is secondary to the inadequate follicular growth. The other 49% of LPD (cycles with normal follicles & LUFs) showed adequate midsecretory (Pattern III). -191- e5ummary If Gonclusion In normal women (control group), 95% were adequate (Pattern III) & 5% were non-adequate (Pattern II). The sensitivity was 51%, the specificity was 95%, the positive predicitive value was 91.1% & the negative predicitive value was 65.9% . * At the late secretory phase (PsOD 12), endometrial echogenicity could detect all the LPD patients. All the cycles (100%) were seen with inadequate late secretory pattern (Pattern II). In normal women (control group), 93% were adequate (Pattern III) & 7% were non-adequate (Pattern II). The sensitivity was 100%, the specificity was 93%, the positive predicitive value was 93.5% & the negative predicitive value was 100% . c- Neither endometrial thickness nor posterior acoustic enhancement was helpful in diagnosis of LPD. Endometrial thickness at day of ovulation (expected ovulation in LUFs), at mid secretory phase (PsOD 7) & at late secretory phase (PsOD 12 or 13), showed non-significant difference in both the study & control groups. Posterior acoustic enbancement was seen in 91% of the cycles of the study group & in 93% of the control group. This difference is insignificant statistically. 8Serum progesterone assay was misleading in diagnosis LPD patients. A single mid-luteal serum progesterone level of 10 ng/ml -192- <Summary’” Gonclusion or more is accepted by most of the authors as adequate for corpus luteum function. All our control group cycles, was seen with lOng/rnl or more (range from 10 to 20.5mg/rnl) . This level was also seen in 68.2% of LPD cycles with normal follicles, (range from 8 to 17 ng/rnl), 49% of LPD cycles with immature follicles (range from 7 to 16 ng/ml) & 20% ofLPD cycles with LUFs (range 7.5 to 15 ng/ml) (totally 56% ofLPD cycles) . • Histologic dating of PEB was very valuable when dating is done in relation to the accurate timing of ovulation determined by ultrasound to- & done by experinced gynaecologic pathologist. Accuracy of dating . I in ~ normal women (control group), was 98%. The error was only in 2% of the cycles & was only one day. The mean out of phase days in LPD cycles with normal follicles was (3.1 ± 0.8), with immature follicles was (6.8 ± 1.5) & in LPD cycles with LUFs was (4.6 ± 0.5).The difference between the cycles were highly significant (P<O.Ol). CONCLUSION: The ideal diagnostic test for LPD patients would involve the PEB & ultrasound evaluation of both follicular growth & endometrial adequacy. PEB is needed for accurate dating of the endometrium to establish the diagnosis & it is necessary to date it in relation to the accurate day -193- <Summary if GoncNsion of ovulation determined by ultrasound & by experinced gynaecologic pathologist . Ultrasound evaluation of the follicular growth is important to detect the main underlying defect in these patients. Either it is a pure luteal phase defect (patients with normal follicles), or secondary to follicular defect which may be due to immature follicles (patients with small size follicles), or due to failure of ovulation (patients with LUFs). Evaluation of endometrial adequacy will be through the study of endometrial echogenicity which is the most promising feature indicating the response of the endometrium to the different circulating hormones. Evaluation of endometrial echogenicity at day of ovulation c is important to evaluate the maturity of the follile whatever its size & . ) foretell us about the adequacy in the mid-secretory phase (PsOD 7). Echogenicity at the mid-secretory phase (PsOD 7) is needed to confirm the result obtained before at day of ovulation or when the patients missed to follow at ovulation. Echogenicity at late secretory phase (PsOD 12 or 13) in considered the most sensitive time for detection of all cases of LPD patients. Ultrasound will not only help in making the diagnosis complete & accurate but also will guide us to the proper treatment of the case which correct the follicular defect & endometrial pattern to achieve adequate endometrial pattern for each corresponding phase of the cycle up to menstruation. The problem of repetition ofPEB could be avoided whenever this adequate pattern is seen. LPD cases with normal follicles will be treated by progesterone support during the luteal phase. LPD -194- .summary & Conclusion cases with immature follicles, the treatment will be through improvement offolliculogensis by clomiphene citrate or HMG. In cases of LUFs, ovulation will be helped either by HCG or by improvement of folliculogensis by clomiphene citrate or HMG with or without HCG. Short luteal phase will be treated by clomiphene citrate. This study is going on now in our Infertility Unit & the results will be published in the near future. We think ultrasound will be more popular in the near future as a diagnostic modality for LPD & with contin~us development of the ultrasonics, the time will come when the sensitivity & specificity become 100%. |