1 University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Cooper Hospital/University Medical Center Department of Obstetrics and Gynecology Division of Reproductive Endocrinology & Infertility, Camden, New Jersey, USA
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Abstract |
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Key words: echo pattern/IVF/luteal phase/sonography
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Introduction |
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The objective of this study was to evaluate the relationship of sonographic assessment of the endometrium in the luteal phase with conception following IVFembryo transfer. Specifically, the relationship between echo pattern 3 days after embryo transfer with conception outcome of IVFembryo transfer in women who have demonstrated adequate endometrial development by the late proliferative phase would be assessed. The hypothesis of this study, based on clinical observations, was that the echo pattern 3 days after embryo transfer associated with the highest pregnancy rates was the HH pattern. The study would further explore whether the use of ovarian stimulation had any influence on pregnancy outcome according to echo patterns 3 days after embryo transfer by comparing pregnancy and implantation rates in oocyte retrieval cycles versus the transfer of frozen embryos.
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Materials and methods |
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Ovarian stimulation for retrieval cycles included the luteal phase leuprolide acetate/gonadotrophin protocol (Wildt et al., 1986; 54 cycles) or the short flare protocol (Barriere et al., 1987
; 32 cycles). Preparation for frozen embryo transfer included down-regulation with leuprolide acetate and oestrogen replacement or oestrogen replacement cycles only. Progesterone was supplemented in the luteal phase of all cycles. The oestrogen replacement consisted of oral micronized oestradiol beginning at 2 mg for 5 days, 4 mg for 4 days, then 6 mg for at least 5 days. Progesterone therapy was added to the oestrogen when the endometrium was at least 8 mm thick and the echo pattern was trilaminar. Progesterone replacement consisted of at least 200 mg progesterone vaginal suppositories twice daily plus 50100 mg i.m. daily of progesterone (US Pharmacopeia). In stimulation cycles, only vaginal progesterone was used.
Embryo transfer was performed if the patient demonstrated adequate endometrial development on the day of human chorionic gonadotrophin (HCG) administration (endometrial thickness 8 mm and a TL or IE echo pattern). Otherwise, all embryos were cryopreserved and transfer deferred. Embryo freezing used a simplified protocol and thawing required only a one-step removal of the cryoprotectant 2-propanediol (Baker et al., 1997). Assisted hatching using acidic Tyrode's solution was performed (Check et al., 1996a
).
The main outcome measures were clinical pregnancy (sonographic evidence of gestational sacs) and implantation rates (number of gestational sacs/embryos transferred) following embryo transfer. Statistical analysis included 2 analysis and t-test for independent groups as appropriate. P < 0.05 was considered to be statistically significant.
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Results |
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Discussion |
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Similarly, the study presented here of endometrial thickness 3 days after embryo transfer did not find that endometrial thickness had much prognostic value. However, similar to previous findings on the day of HCG, the sonographic echo patterns were related to the establishment of clinical pregnancies in fresh embryo transfers. In contrast to the mid-cycle data, the echo pattern with the adverse prognosis was the non-homogeneous hyperechogenic pattern 3 days after transfer.
The mechanism for failure to change from triple line to homogeneous hyperechogenic pattern is not known. There was no relationship with the mid-luteal phase serum progesterone values and type of echo pattern. Other studies have not shown any relationship with the mid-luteal phase triple line echo pattern and the out-of-phase endometrial biopsy (Grunfeld et al., 1991; Doherty et al., 1993
; Ficicioglu et al., 1995
; Sterzik et al., 1997
). Possibly, future studies may find some relationship of the triple line echo pattern and endometrial oestrogen and progesterone receptors or their ratio. A study by Ohno and Fujimoto did not find any relationship with the pre-ovulatory echo appearance and endometrial steroid hormone receptor concentration (Ohno and Fujimoto, 1998
). However, the ratio of progesterone:oestrogen receptor concentration was somewhat less when a triple line pattern was not seen in the pre-ovulatory endometrium (Ohno and Fujimoto, 1998
).
The significant difference in serum LH at mid-cycle in frozen embryo transfer cycles between those with HH and non-HH patterns was interesting. Indeed, some studies have suggested poor pregnancy rates with higher follicular phase serum LH concentrations (Adams et al., 1986; Homburg et al., 1988
; Polson et al., 1988
; Regan et al., 1990
), though other studies did not agree (Check et al., 1996b
). In this study the pre-ovulatory LH concentrations were the highest in the group with the HH pattern who have the best pregnancy prognosis. Furthermore, no such relationship with LH and luteal phase echo patterns post-transfer was observed in cycles where oocyte retrieval occurred. No other relationships were noted in stimulated cycles or frozen embryo transfer cycles with any other hormonal concentrations and echo patterns.
There is evidence that ovarian stimulation regimen may have an adverse effect on implantation (Check et al., 1995, 1999
). The fact that 28 of 86 (32.5%) patients having oocyte retrievals had a non-HH pattern 3 days post-transfer versus only 11 out of 86 (12.7%) having frozen embryo transfer could suggest that at least some individuals with adverse implantation factors following ovarian stimulation can be identified by observing a non-HH pattern in the luteal phase. At least in subsequent treatment cycles, it may seem reasonable to cryopreserve all embryos for future frozen embryo transfer when a non-HH pattern occurs 3 days after transfer. Unfortunately, since this study required that the same individual could not be used for a fresh and frozen embryo transfer cycle, it cannot be determined from these data if women with non-HH patterns following ovarian stimulation have much less chance of this happening with frozen embryo transfer. Thus, an interesting future study would be to determine the percentage of a non-HH pattern 3 days after transfer following randomization to a fresh or frozen embryo transfer from women who had a non-HH pattern in their first retrieval cycle.
Future studies should probably also include measurement of uterine and subendometrial blood flow in stimulated and non-stimulated cycles and the association with HH and non-HH patterns 3 days after transfer. Though the numbers were too small to make a conclusive statement, not only was a non-HH pattern less common with frozen embryo transfer cycles, but the non-HH pattern was not associated with a decreased pregnancy or implantation rate. Why the adverse effects of ovarian stimulation seem to relate, at least in part, to a non-HH pattern 3 days after transfer, even though this pattern does not seem to impair pregnancies in frozen embryo transfer cycles, is not known. Possibly this information may help to elucidate in the future the mechanism by which the stimulation regimen may impair implantation.
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Notes |
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References |
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Submitted on October 4, 1999; accepted on January 24, 2000.