In Vitro Fertilization-embryo Transfer Treatment Research Articles

Influence of endometrial thickness and pattern on pregnancy rates in in vitro fertilization-embryo transfer.

Aim : Our aim was to investigate the role of endometrial thickness and pattern in the pregnancy rate during an in vitro fertilization-embryo transfer (IVF-ET) cycle. Methods : Records of patients who underwent IVF-ET at the Jichi Medical School Hospital during May 1995-December 1999 were evaluated retrospectively. Only cycles, in which endometrial thickness and pattern on the day of human chorionic gonadotrophin (HCG) administration were recorded, were analyzed in this study. Endometrial thickness was divided into three categories (A:<10mm, B: 10-14mm, C:>14mm), and endometrial pattern was divided into two categories: triple line and non-triple line. A total of 156 IVF-ET cycles from 120 patients was evaluated. Results : There were no significant differences for both the endometrial thickness and pattern in the pregnancy rate during the IVF-ET cycle (P>0.05). Among the study groups, the triple-line endometrial pattern was found to be 58.7% in group A, 84.0% in group B and 70% in group C. We found that in the triple-line endometrial pattern, there was a significant difference between group A and group B (P<0.01). Triple-line endometrial pattern appeared significantly in younger women (33±5.4years) than in non-triple-line endometrial pattern (36±5.2years; P=0.047). The minimum and maximum endometrial thickness where pregnancy occurred was 6.5mm (two pregnancies) and 19mm (one pregnancy), respectively. Conclusion : Endometrial thickness and pattern have no influence on the pregnancy rates in an IVF-ET cycle, but patients with triple-line endometrial pattern and group B endometrial thickness showed a better pregnancy outcome in the IVF-ET treatment. (Reprod Med Biol 2002; 1: 17-21).

Embryo transfer and uterine junctional zone contractions.

Embryo transfer is one of the most critical steps affecting the success rate of in-vitro fertilization (IVF) and has changed little since IVF was first described (Steptoe and Edwards 1978). While there is general agreement that a smooth embryo transfer is associated more frequently with successful outcome (Wood et al., 1985; Mansour et al., l990; Visser et al., 1993; Tomas et al., 1998) this opinion is not unanimous (Nabi et al., l997; Tur-Kaspa et al., l998). However, embryos have been found in the vagina following embryo transfer (Poindexter et al., l986; Schulman, 1986) and experimental studies of mock embryo transfer in humans showed expulsion of Methylene Blue in 57% of transfers (Mansour et al., l994) and movement of X-ray contrast medium towards the Fallopian tubes and cervix/vagina in 38 and 21% respectively (Knutzen et al., 1992). Uterine junctional zone (JZ) contractions or endometrial wavelike movements have been characterized in both natural (Ijland et al., 1996, 1997a,b; Kunz and Leyendecker, 1996) and assisted reproduction cycles (Lesny et al., l998b). Recently increased contractility before embryo transfer has been shown to be associated with a lower pregnancy rate (Fanchin et al., 1998). As JZ contractility is minimal and progressively decreases during the luteal phase (Ijland et al., 1996; Lesny et al., 1998b), interference with the endometrium at embryo transfer may change the contraction pattern and affect implantation in a mechanical way. The observation of JZ contractions after mock embryo transfer in oocyte donors (Lesny et al., l998a) provides information about possible treatment outcome. It also demonstrates a connection between the ease of transfer, JZ contractions and mobility of mock embryos in utero. An atraumatic embryo transfer (with a soft end of the catheter, without touching the uterine fundus) did not have any effect on JZ contractility or movement of the mock embryo (Echovist). Difficult embryo transfers (mimicked by touching twice the uterine fundus with soft end of the catheter) generate strong fundo–cervical and random waves in the fundal area which were able to relocate mock embryos towards the cervix and/or into the intramural segment of the Fallopian tube. Contractions were also present when we stimulated uterus with the softer version of the catheter but their effect on mock embryos was to a lesser extent. We chose fundal stimulation because in our opinion it was the most frequent type of stimulus unwillingly given to the uterus at embryo transfer and is not usually considered as a problem. Moreover, we also noted that the application of a tenaculum to the cervix, as occasionally used during embryo transfer to correct the uterine position, could trigger JZ contractions (Lesny et al., 1998c). A further analysis of our 6 years clinical data revealed that an ectopic pregnancy was 3.9 times (95% CI from 1.5 to 10.2) more frequently associated with a difficult embryo transfer than with an easy procedure (Lesny et al., 1998d). In conclusion, the above facts confirm the existence of a mechanical force, which can be one of the decisive factors for embryos to remain in utero. Junctional zone contractions and endometrial wavelike movements of adjacent endometrium can provide an explanation for several clinical facts like lower success rate after difficult embryo transfer or higher ectopic and heterotopic pregnancy rates after IVF–embryo transfer treatment. They also highlight a need for atraumatic embryo transfer without touching the uterine fundus and without manipulation within the cervical area. The benefits arising from using softer catheters or pharmacological assistance at the time of embryo transfer remain to be tested.

Influence of antithyroid antibodies in euthyroid women on in vitro fertilization-embryo transfer outcome.

To investigate whether antithyroid antibodies (ATAs) affect the pregnancy outcome in euthyroid women undergoing in vitro fertilization-embryo transfer (IVF-ET). Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody (TGA) were measured by radioligand assay kits that were used as ATAs in 79 patients with tubal or unexplained infertility who were enrolled in an IVF-ET program. Women who were positive for antinuclear antibody, lupus anticoagulant, anticardiolipin antibody, and rheumatoid factor were excluded from our study. The study group comprised 28 (29.1%) euthyroid women who were positive for TPOAs, TGAs, or both. Fifty-one euthyroid women without ATAs served as control subjects. The results were analyzed with linear regression analysis, Student's t-test, Mann-Whitney U test, Kruskal-Wallis analysis of variance, chi 2 test, and Fisher's exact test. There were no significant differences between the study group and the control group in patient characteristics such as age, infertility duration, and hormonal profile. There were also no significant differences between the two groups with respect to the number of retrieved oocytes, the fertilization rate, the number of embryos frozen, and the number of embryos transferred. There were no correlations between ATA (TPOA and TGA) titers and the fertilization rate. The clinical pregnancy rate per cycle was significantly lower in the study group, with 26.3% (10/38), compared with 39.3% (35/89) in the control group. The biochemical pregnancy rate per cycle and the miscarriage rate were significantly higher in the study group, 18.4% (7/38) and 40.0% (4/10), respectively, compared with 5.6% (5/89) and 11.4% (4/35), respectively, in the control group. In the study group, both TPOA and TGA titers were significantly higher in the biochemical pregnancy group than in the clinical pregnancy group or the nonpregnancy group. In 10 women with ATAs who achieved pregnancy after IVF-ET, both TPOA and TGA titers were significantly higher in the miscarriage group than in the ongoing pregnancy/delivery group. ATAs in euthyroid women with tubal or unexplained infertility have an association with a poor pregnancy outcome after IVF-ET treatment.

Altered peripheral benzodiazepine receptor density in human granulosa-lutein cells in relation to follicular maturity

Since the introduction of treatment by in vitro fertilization/ embryo transfer (IVF-ET) in humans, a harmless approach to identifying the ovum with a greater chance of producing an implantable embryo has been sought worldwide. Our previous studies indicated a high correlation between degree of follicular maturation and benzodiazepine (BZ) receptor density in rats. We hypothesized that if such a correlation existed in humans, the latter might be used to evaluate degree of follicular maturation and, consequently, its corresponding oocyte competence. We used [ 3H]PK 11195, a ligand selective to peripheral BZ receptors, to determine their density in human granulosa-lutein (G-L) cells. [ 3H]PK 11195 bound to G-L cells with high affinity in a saturable manner. Scatchard analysis revealed the presence of a single population of receptors. The average equilibrium dissociation constant and maximal number of receptors (B max) measured in G-L cells were 3.4 ± 0.2 nM and 608 ± 61 fmol/mg protein, respectively. In G-L cells obtained from individual follicles, a significant increase in the specific binding to peripheral BZ receptors was noted in G-L cells of follicles yielding oocytes at an advanced stage of cumulus maturation or oocytes competent for fertilization and subsequent cleavage. When G-L cells were pooled from all the follicles of each individual woman, the average B max value of [ 3H]PK 11195 in G-L cells was 900 ± 127 fmol/mg protein in women who conceived, which was 80% higher ( P < 0.01) than in women who did not conceive. We suggest that the remarkable increase in peripheral BZ receptor density in the G-L cells of individual follicles yielding fertilizable oocytes and in G-L cells of women who conceived should be considered as a fast and convenient predictor of the chance of pregnancy with human IVF-ET treatment.

Levels of Steroid-Binding Proteins and Steroids in Human Preovulatory Follicle Fluid and Serum as Predictors of Success inin VitroFertilization-Embryo Transfer Treatment*

In an attempt to identify the embryos and cycles that have the best chances of resulting in establishment of pregnancies, after in vitro fertilization-embryo transfer (IVF-ET) treatment, the concentrations of sex hormone-binding globulin (SHBG) and cortisol-binding protein (CBP) were measured, using two new enzyme-linked immunosorbent assays in serum and follicle fluid (FF) from 30 women (125 FF) undergoing IVF-ET. The concentrations were compared to those of total estradiol and total progesterone, and correlated to oocyte cleavage and the establishment of pregnancies. Serum concentrations of CBP were significantly higher in women who became pregnant (1469 +/- 108) nM (+/- SEM] than in those who did not (CBP, 1200 +/- 58 nM; P less than or equal to 0.05). The concentrations of SHBG were not significant different in these two groups of women (72.4 +/- 9.3 and 60.8 +/- 4.2 nM, respectively; P greater than or equal to 0.10). By contrast, in FF significantly higher concentrations of both SHBG and CBP were found in women achieving pregnancy (SHBG, 56.1 +/- 2.8 nM; CBP, 1198 +/- 37 nM) than in those who did not (SHBG, 45.5 +/- 1.4 nM; P less than or equal to 0.001; CBP, 1079 +/- 29 nM; P less than or equal to 0.01). A positive correlation was found between serum and FF levels of both SHBG (r = 0.85; P less than or equal to 0.001) and CBP (r = 0.70; P less than or equal to 0.001). FF levels of estradiol and progesterone did not differ regardless of whether the oocyte cleaved. However, a significant reduction of estradiol was found in fluid from follicles in which the oocyte cleaved and resulted in pregnancy (3046 +/- 180 nM) than in fluid from follicles in which the oocyte cleaved but without establishment of pregnancy (4162 +/- 282 nM; P less than or equal to 0.001). There was no correlation between estradiol and SHBG and between progesterone and CBP. However, levels of FF progesterone above 15,000 nM combined with CBP concentrations above the mean concentration found in FF (1,127 nM) were related with oocyte cleavage in 87% of the cases. The overall cleavage rate is 56%. The higher levels of SHBG and CBP in serum compared to those in FF, and the positive relationship between serum and FF levels suggest that both proteins arise from the circulation. The similar levels in serum and FF indicate that neither SHBG nor CBP is responsible for maintaining the concentration gradient of estradiol and progesterone from follicle to plasma.(ABSTRACT TRUNCATED AT 400 WORDS)