Factors affecting embryo implantation after human in vitro fertilization: A hypothesis RichardJ. Paulson, MD, Mark V. Sauer, MD, and Rogerio A. Lobo, MD Los Angeles, California In the clinical practice of human in vitro fertilization, pregnancy is dependent on embryo implantation. Pregnancy is a function of the number of embryos transferred, with multiple embryos resulting in a higher likelihood of pregnancy. We formulated a mathematic model of embryo implantation. This model describes embryo implantation as dependent on three factors-transfer efficiency, embryo quality, and endometrial receptivity. Application of existing embryo implantation data to this model allows the calculation of the approximate value of each of these factors. On the basis of historic data, data obtained from our in vitro fertilization program, and these theoretic considerations, it is our hypothesis that (1) there is an inherent inefficiency associated with the mechanical transfer of embryos into the uterine cavity, which limits the maximal embryo implantation rate; (2) the quality of embryos produced by controlled ovarian hyperstimulation, follicle aspiration, and in vitro fertilization is very high and approaches that of embryos produced in natural cycles in vivo; and (3) endometrial receptivity is markedly diminished in stimulated cycles and is the current rate-limiting step of pregnancy success of in vitro fertilization. (AM J OBSTET GVNECOL 1990;163:2020-23.)
Key words: Embryo implantation, in vitro fertilization, unstimulated in vitro fertilization, endometrial receptivity, oocyte donation
In the clinical practice of human in vitro fertilization (IVF) the majority of pregnancy failures occurs after embryo transfer. Whereas the majority of patients achieve oocyte recovery, fertilization, and cleavage of embryos, only a small proportion of transferred embryos actually implant and result in viable pregnancies. Thus pregnancy after IVF and embryo transfer is dependent on embryo implantation. Furthermore, the pregnancy rate is known to increase when multiple embryos are transferred. I It has been suggested that in the first approximation, embryo implantation can be treated as an independent event! When multiple embryos are transferred, the implantation of one embryo neither inhibits nor enhances the implantation of any of the other embryos. This assumption leads to the equation:
P = 1 - (l - EI)" where P is pregnancy, EI is the likelihood of implantation of an individual embryo, and n is the number of embryos transferred. 2 From the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, and California Reproductive Health Institute, California Medical Center. Presented at the Thirty-seventh Annual Meeting of the Society for Gynecologic Investigation, St. Louis, Missouri, March 21 to 24, 1990. Reprint requests: Richard]. Paulson, MD, Women's Hospital, Room L-1022, 1240 N. Mission Road, Los Angeles, CA 90033. 6/6/24778
2020
We developed a mathematic model for embryo implantation based on the tenet that embryo implantation is an independent event and we described embryo implantation as consisting of three separate components with individual values that vary under specific clinical conditions. The purpose of this article is to present our mathematic model of factors that affect embryo implantation, to analyze available embryo implantation data in an effort to test and validate this model, and to determine the relative contribution of each of the putative factors under specific clinical conditions.
Material and methods To develop our hypothesis of factors that affect embryo implantation, we followed three steps. First, we considered previous mathematic formulations and expounded on them. Second, we used embryo implantation data from published sources to modify our model and to help express a maximal attainable rate for embryo implantation. Finally, we examined embryo implantation data from three groups of patients in our own IVF program to test our hypothesis and to assign specific values to the components of the embryo implantation equation. Hypothesis. The concepts of embryo quality and endometrial receptivity have been used to describe pregnancy success 2. 3 : Embryo implantation = Embryo quality x endometrial receptivity
Embryo implantation in in vitro fertilization
Volume 163 Number 6, Part 1
Whereas ideal embryo quality and endometrial receptivity may inevitably lead to embryo implantation in vivo, we do not believe that the same will occur when embryos undergo extracorporeal manipulation and mechanical transfer to the uterus. Therefore we chose to group the factors that affect embryo implantation into three general categories including the previously introduced concepts of embryo quality and endometrial receptivity and add a third term, that of transfer efficiency. The latter term quantifies the failure of embryo implantation resulting from the embryo transfer process itself. Thus in the first formulation we have: Embryo implantation = Embryo quality X endometrial receptivity X transfer efficiency Transfer efficiency. Transfer efficiency is a term that may be different under different circumstances. It may vary with transfer catheters, the position of the patient, the clinician who performs the transfer, and the different routes of embryo transfer, such as transcervical versus the fallopian tubes. Therefore in estimating this value we chose to focus on implantations after embryo transfer by the transcervical route because this is the most commonly used technique in both our program and in most other institutions. Because transfer efficiency is equal to embryo implantation when both embryo quality and endometrial receptivity are optimal, we thought the best approximation to this value would be obtained by examination of the implantation rates after the synchronous transfer in natural cycles of in vivo fertilized blastocysts. We are aware of two published series in human beings that address this issue. 4 • 5 Buster et al! reported implantations in two of four blastocysts transferred. Formigli et al. 5 reported implantations in four of six expanded blastocysts transferred and in six of II embryos transferred at the morula stage or thereafter, suggesting a range of 50% to 67% for transfer efficiency in human patients. In animals, reported embryo implantation rates after transcervical transfer of in vivo fertilized blastocysts obtained by uterine flushing are in the range of 50% to 75%.6 Therefore as a best estimate we believe that with experienced clinicians the approximate value of transfer efficiency for transcervical embryo transfer is 60%. After updating our formula we now have: Embryo implantation
Transfer efficiency X embryo quality X endometrial receptivity Transfer efficiency = 0.6 Embryo implantation = 0.60 X embryo quality X endometrial receptivity =
Embryo quality. Because an in vivo fertilized blastocyst is considered to have an embryo quality value of
2021
1, and not all 48-hour embryos become blastocysts, a correction term is needed to account for the clinical practice of transferring embryos 48 hours after follicle aspiration. This term is the percentage of 2-day embryos that progress to the blastocyst stage and provides the maximum quality value that can be assigned to an embryo after 48 hours of development. In the most commonly used animal model, the mouse, in vivo fertilized embryos collected at the 1- or 2-cell stage progress to blastocyst in about 75% of cases. 7 In human beings, IVF embryo freezing studies reported about a 25% progression to blastocyst, although this number would probably be higher if all embryos were cultured rather than only those that remain after fresh embryo transfer. 8 On the basis of these admittedly scant data, we chose to estimate the percent progression to blastocyst of 48-hour old human embryos at 60%. Restatement of our original formula: Embryo implantation = Transfer efficiency X embryo quality x endometrial receptivity Embryo quality . = 0.6 X embryo quahty (correcte d) (Transfer efficiency = 60%, as stated in the preceding section) With these estimates, Embryo implantation = 0.36 X embryo quality X endometrial receptivity and thus when embryo quality and endometrial receptivity are optimized, Embryo implantation = 36% With this theoretic formulation, we now analyzed embryo implantation data from our IVF program in an effort to test and apply our hypothesis. Patient selection. Embryo implantation data was obtained in a retrospective fashion from three groups of patients in our program. 9"" Our non anonymous donor oocyte program provides a unique model of embryo implantation because it is conducted in a manner identical to standard IVF.9 In particular, ovarian stimulation and follicle aspiration regimens are identical and all resultant embryos are available for transfer and thus provide embryos of quality similar to that of standard IVF. Embryos are transferred to the uteri of agonadal recipients receiving exogenous estradiol and progesterone whose endometrial histology is synchronous as proved by biopsy in a prior replacement cycle. A total of 18 cycles were conducted between January 1988 and June 1989 with donors who were 35 years old or younger and who had conceived at least once previously. From our standard IVF program, we selected for analysis cycles that we thought would result in embryo quality identical"to that of the donor cycles. 10 We considered only patients who were 35 years old or younger, who
2022
Paulson, Sauer, and Lobo
December 1990 Am J Obstet Gynecol
Table I. Embryo implantation data Embryos transferred No.
dIVFt (n = 18) 75 sIVF§ (n = 54) 225 uIVFII (n = 24) 24
1% per cycle 4.2 4.2 1.0
Implantations*
Clinical pregnancies
No.
No·1 %
26 24 5
1% 35
IU
21
12 21 5
67* 39 21
*Total number of gestational sacs observed by transvaginal ultrasonographic examination in each group and the percentage of likelihood of implantation of an individual embryo. tDonor oocyte IVF group.g· 10 *p < 0.05 vs other groups. §Standarad IVF group; patients were matched to donors in the donor oocyte IVF group. lO II Unstimulated cycles triggered with heG. Only embryos derived from successfully aspirated dominant follicles were considered."
had conceived at least once previously, and in whom pelvic factor was the sole or predominant cause of infertility. A total of 54 such cycles were conducted during the same 18-month period. These data were previously reported in detaiJ.1° The third group consisted of patients undergoing embryo transfer in unstimulated IVF cycles during January 1988 to December 1989. The unstimulated IVF protocol was previously described. 11.12 Briefly, it is offered to normally ovulatory patients with pelvic factor whose follicular development in a spontaneous cycle is monitored with serial ultrasonographic examination. Human chorionic gonadotropin (hCG) is administered when the follicle reaches maturity criteria. In this analysis, we considered only the 24 cycles in which embryos that resulted from successfully aspirated dominant follicles were transferred.
Results Table I depicts the total number of embryos transferred, the total number of implantations, the individual embryo implantation rate, and the clinical pregnancy rate in the donor oocyte, standard, and unstimulated IVF groups.9," As a result of the matching between the donor and standard IVF groups, a similar number of embryos of similar morphologic quality were obtained and transferred in each of these cycles. lo In the donor group, 75 total embryos were transferred and 26 implanted, for an embryo implantation rate of 35% and a clinical pregnancy rate of 67%. In the standard IVF group, 225 embryos were transferred and 24 of these were implanted for an embryo implantation rate of 11 % and a clinical pregnancy rate of 39%. These differences are statistically significant (p < 0.05). In the unstimulated group, 24 transferred embryos resulted in five implantations or a 21 % implantation rate, which was significantly higher than that of the stimulated cycles (p < 0.05). (Clinical pregnancy rates are presented
for completeness but are not included in the implantation analysis.)
Comment Values for embryo quality and endometrial receptivity can now be approximated. In the donor IVF group: Embryo implantation = 0.35 Embryo implantation = 0.36 x embryo quality x endometrial receptivity implying that Embryo quality - 1 Embryo receptivity - 1 That endometrial recptivity is optimal is not surprising because the endometrial histology had been optimized. However, if embryo quality is also optimal, this means that current stimulation regimens are capable of producing embryos of a quality that is, at least among those embryos selected for transfer, comparable to that of embryos produced in vivo during natural cycles. In the standard IVF group: Embryo implantation = 0.11 Embryo implantation = 0.36 x embryo quality x endometrial receptivity thus Embryo quality x endometrial receptivity - 0.33 However, by design: Embryo quality (standard IVF) = Embryo quality (donor IVF) = 1 implying that Embryo receptivity (standard IVF) = 0.33 This difference in endometrial receptivity between standard IVF and donor IVF cycles implies that in stimulated cycles, endometrial receptivity is the principal limiting factor of embryo implantation lO and that as many as two thirds of transferred embryos capable of implanting fail to do so as a result of decreased endometrial receptivity. In the unstimulated IVF group: Embryo implantation = 21 % Embryo implantation = 0.36 x embryo quality x endometrial receptivity thus Embryo quality x endometrial receptivity
=
0.60
There is no clear way to assign relative value to embryo quality and endometrial receptivity in this case. However, because steroid levels and their patterns of change in these cycles are essentially natural, it seems
Embryo implantation in in vitro fertilization
Volume 163 Number 6, Part I
reasonable to assume that endometrial receptivity is uncompromised. If that is true, then Embryo quality = 0.60 Because hCG is administered in these cycles before the onset of the luteinizing hormone surge, this diminished embryo quality value may be explained as reflective of incorrect timing of hCG administration, with resultant diminished oocyte quality. Our formula and the derived approximate values for transfer efficiency, embryo quality, and endometrial receptivity are not to be taken literally. Rather, it is our intent to attempt to explain the differences in embryo implantation rates that we observed in our program and in the reports of others. We believe that the concept of transfer efficiency is an important addition to the previously introduced embryo quality and endometrial receptivity and may help to explain some of the differences in implantation rates observed under different clinical circumstances and help to define a maximal embryo implantation rate. We also tried to extrapolate from available data the approximate value of the maximal embryo implantation rate that can be expected with current techniques. We estimated this value at 36%. This number matches closely the embryo implantation rates observed in our donor oocyte IVF program. This observation led us to the conclusion that selected embryos obtained from fertilization in vitro of oocytes obtained from hyperstimulated cycles are of a quality that approximates that of in vivo fertilized embryos in natural cycles. Under the scrutiny of time and as additional data become available, the approximate values in this article will likely have to be modified. We present them as a first approximation and as a stimulus to further exploration of this topic.
2023
REFERENCES I. In vitro fertilization/ embryo transfer in the United States: 1988 results from the National IVF-ET registry. Fertil SteriI1990;53:13. 2. Walters DE, Edwards RG, Meistrich ML. A statistical evaluation of im plantation after replacing one or more human embryos. J Reprod Fertil 1985;74:557. 3. Rogers PAW, Milne BJ, Trounson AO. A model to show human uterine receptivity and embryo viability following ovarian stimulation for in vitro fertilization. J In Vitro Fert Embryo Transfer 1986;3:93. 4. Buster JE, Bustillo M, Thorneycroft IH, et al. Nonsurgical transfer of in vivo fertilized donated ova to five infertile women: report of two pregnancies. Lancet 1983;2:223. 5. Formigli L, Formigli G, Roccio C. Donation of fertilized uterine ova to infertile women. Fertil SterilI987;47:162. 6. Anderson GB. Embryo transfer in domestic animals. Adv Vet Sci Comp Med 1983;27:129. 7. Davidson A, Vermesh M, Lobo RA, Paulson RJ. Mouse embryo culture as quality control for human in vitro fertilization: the one versus two-cell model. Fertil Steri11988; 49:516. 8. Fehilly CB, CohenJ, Simons RF, Fishel SB, Edwards RG. Cryopreservation of cleaving embryos and expanded blastocysts in the human: a comparative study. Fertil Steril 1985;44:638. 9. Sauer MV, Paulson Rj, Macaso TM, Francis-Hernandez M, Lobo RA. Establishment of a nonanonymous donor oocyte program: preliminary experience at the University of Southern California. Fertil Steril 1989;52:433. 10. Paulson RJ, Sauer MV, Lobo RA. Embryo implantation following human in vitro fertilization: importance of endometrial receptivity. Fertil Steril 1990;53:870. II. Paulson RJ, Sauer MV, Francis MM, Macaso TM, Lobo RA. In vitro fertilization in unstimulated cycles [Abstract 437]. In: Proceedings of the thirty-seventh annual meeting of the Society for Gynecologic Investigation, St. Louis, March 21-24, 1990. 12. Paulson RJ, Sauer MV, Lobo RA. In vitro fertilization in unstimulated cycles: a new application. Fertil Steril 1989; 51:1059.
Key words: Embryo implantation, in vitro fertilization, unstimulated in vitro fertilization, endometrial receptivity, oocyte donation
In the clinical practice of human in vitro fertilization (IVF) the majority of pregnancy failures occurs after embryo transfer. Whereas the majority of patients achieve oocyte recovery, fertilization, and cleavage of embryos, only a small proportion of transferred embryos actually implant and result in viable pregnancies. Thus pregnancy after IVF and embryo transfer is dependent on embryo implantation. Furthermore, the pregnancy rate is known to increase when multiple embryos are transferred. I It has been suggested that in the first approximation, embryo implantation can be treated as an independent event! When multiple embryos are transferred, the implantation of one embryo neither inhibits nor enhances the implantation of any of the other embryos. This assumption leads to the equation:
P = 1 - (l - EI)" where P is pregnancy, EI is the likelihood of implantation of an individual embryo, and n is the number of embryos transferred. 2 From the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, and California Reproductive Health Institute, California Medical Center. Presented at the Thirty-seventh Annual Meeting of the Society for Gynecologic Investigation, St. Louis, Missouri, March 21 to 24, 1990. Reprint requests: Richard]. Paulson, MD, Women's Hospital, Room L-1022, 1240 N. Mission Road, Los Angeles, CA 90033. 6/6/24778
2020
We developed a mathematic model for embryo implantation based on the tenet that embryo implantation is an independent event and we described embryo implantation as consisting of three separate components with individual values that vary under specific clinical conditions. The purpose of this article is to present our mathematic model of factors that affect embryo implantation, to analyze available embryo implantation data in an effort to test and validate this model, and to determine the relative contribution of each of the putative factors under specific clinical conditions.
Material and methods To develop our hypothesis of factors that affect embryo implantation, we followed three steps. First, we considered previous mathematic formulations and expounded on them. Second, we used embryo implantation data from published sources to modify our model and to help express a maximal attainable rate for embryo implantation. Finally, we examined embryo implantation data from three groups of patients in our own IVF program to test our hypothesis and to assign specific values to the components of the embryo implantation equation. Hypothesis. The concepts of embryo quality and endometrial receptivity have been used to describe pregnancy success 2. 3 : Embryo implantation = Embryo quality x endometrial receptivity
Embryo implantation in in vitro fertilization
Volume 163 Number 6, Part 1
Whereas ideal embryo quality and endometrial receptivity may inevitably lead to embryo implantation in vivo, we do not believe that the same will occur when embryos undergo extracorporeal manipulation and mechanical transfer to the uterus. Therefore we chose to group the factors that affect embryo implantation into three general categories including the previously introduced concepts of embryo quality and endometrial receptivity and add a third term, that of transfer efficiency. The latter term quantifies the failure of embryo implantation resulting from the embryo transfer process itself. Thus in the first formulation we have: Embryo implantation = Embryo quality X endometrial receptivity X transfer efficiency Transfer efficiency. Transfer efficiency is a term that may be different under different circumstances. It may vary with transfer catheters, the position of the patient, the clinician who performs the transfer, and the different routes of embryo transfer, such as transcervical versus the fallopian tubes. Therefore in estimating this value we chose to focus on implantations after embryo transfer by the transcervical route because this is the most commonly used technique in both our program and in most other institutions. Because transfer efficiency is equal to embryo implantation when both embryo quality and endometrial receptivity are optimal, we thought the best approximation to this value would be obtained by examination of the implantation rates after the synchronous transfer in natural cycles of in vivo fertilized blastocysts. We are aware of two published series in human beings that address this issue. 4 • 5 Buster et al! reported implantations in two of four blastocysts transferred. Formigli et al. 5 reported implantations in four of six expanded blastocysts transferred and in six of II embryos transferred at the morula stage or thereafter, suggesting a range of 50% to 67% for transfer efficiency in human patients. In animals, reported embryo implantation rates after transcervical transfer of in vivo fertilized blastocysts obtained by uterine flushing are in the range of 50% to 75%.6 Therefore as a best estimate we believe that with experienced clinicians the approximate value of transfer efficiency for transcervical embryo transfer is 60%. After updating our formula we now have: Embryo implantation
Transfer efficiency X embryo quality X endometrial receptivity Transfer efficiency = 0.6 Embryo implantation = 0.60 X embryo quality X endometrial receptivity =
Embryo quality. Because an in vivo fertilized blastocyst is considered to have an embryo quality value of
2021
1, and not all 48-hour embryos become blastocysts, a correction term is needed to account for the clinical practice of transferring embryos 48 hours after follicle aspiration. This term is the percentage of 2-day embryos that progress to the blastocyst stage and provides the maximum quality value that can be assigned to an embryo after 48 hours of development. In the most commonly used animal model, the mouse, in vivo fertilized embryos collected at the 1- or 2-cell stage progress to blastocyst in about 75% of cases. 7 In human beings, IVF embryo freezing studies reported about a 25% progression to blastocyst, although this number would probably be higher if all embryos were cultured rather than only those that remain after fresh embryo transfer. 8 On the basis of these admittedly scant data, we chose to estimate the percent progression to blastocyst of 48-hour old human embryos at 60%. Restatement of our original formula: Embryo implantation = Transfer efficiency X embryo quality x endometrial receptivity Embryo quality . = 0.6 X embryo quahty (correcte d) (Transfer efficiency = 60%, as stated in the preceding section) With these estimates, Embryo implantation = 0.36 X embryo quality X endometrial receptivity and thus when embryo quality and endometrial receptivity are optimized, Embryo implantation = 36% With this theoretic formulation, we now analyzed embryo implantation data from our IVF program in an effort to test and apply our hypothesis. Patient selection. Embryo implantation data was obtained in a retrospective fashion from three groups of patients in our program. 9"" Our non anonymous donor oocyte program provides a unique model of embryo implantation because it is conducted in a manner identical to standard IVF.9 In particular, ovarian stimulation and follicle aspiration regimens are identical and all resultant embryos are available for transfer and thus provide embryos of quality similar to that of standard IVF. Embryos are transferred to the uteri of agonadal recipients receiving exogenous estradiol and progesterone whose endometrial histology is synchronous as proved by biopsy in a prior replacement cycle. A total of 18 cycles were conducted between January 1988 and June 1989 with donors who were 35 years old or younger and who had conceived at least once previously. From our standard IVF program, we selected for analysis cycles that we thought would result in embryo quality identical"to that of the donor cycles. 10 We considered only patients who were 35 years old or younger, who
2022
Paulson, Sauer, and Lobo
December 1990 Am J Obstet Gynecol
Table I. Embryo implantation data Embryos transferred No.
dIVFt (n = 18) 75 sIVF§ (n = 54) 225 uIVFII (n = 24) 24
1% per cycle 4.2 4.2 1.0
Implantations*
Clinical pregnancies
No.
No·1 %
26 24 5
1% 35
IU
21
12 21 5
67* 39 21
*Total number of gestational sacs observed by transvaginal ultrasonographic examination in each group and the percentage of likelihood of implantation of an individual embryo. tDonor oocyte IVF group.g· 10 *p < 0.05 vs other groups. §Standarad IVF group; patients were matched to donors in the donor oocyte IVF group. lO II Unstimulated cycles triggered with heG. Only embryos derived from successfully aspirated dominant follicles were considered."
had conceived at least once previously, and in whom pelvic factor was the sole or predominant cause of infertility. A total of 54 such cycles were conducted during the same 18-month period. These data were previously reported in detaiJ.1° The third group consisted of patients undergoing embryo transfer in unstimulated IVF cycles during January 1988 to December 1989. The unstimulated IVF protocol was previously described. 11.12 Briefly, it is offered to normally ovulatory patients with pelvic factor whose follicular development in a spontaneous cycle is monitored with serial ultrasonographic examination. Human chorionic gonadotropin (hCG) is administered when the follicle reaches maturity criteria. In this analysis, we considered only the 24 cycles in which embryos that resulted from successfully aspirated dominant follicles were transferred.
Results Table I depicts the total number of embryos transferred, the total number of implantations, the individual embryo implantation rate, and the clinical pregnancy rate in the donor oocyte, standard, and unstimulated IVF groups.9," As a result of the matching between the donor and standard IVF groups, a similar number of embryos of similar morphologic quality were obtained and transferred in each of these cycles. lo In the donor group, 75 total embryos were transferred and 26 implanted, for an embryo implantation rate of 35% and a clinical pregnancy rate of 67%. In the standard IVF group, 225 embryos were transferred and 24 of these were implanted for an embryo implantation rate of 11 % and a clinical pregnancy rate of 39%. These differences are statistically significant (p < 0.05). In the unstimulated group, 24 transferred embryos resulted in five implantations or a 21 % implantation rate, which was significantly higher than that of the stimulated cycles (p < 0.05). (Clinical pregnancy rates are presented
for completeness but are not included in the implantation analysis.)
Comment Values for embryo quality and endometrial receptivity can now be approximated. In the donor IVF group: Embryo implantation = 0.35 Embryo implantation = 0.36 x embryo quality x endometrial receptivity implying that Embryo quality - 1 Embryo receptivity - 1 That endometrial recptivity is optimal is not surprising because the endometrial histology had been optimized. However, if embryo quality is also optimal, this means that current stimulation regimens are capable of producing embryos of a quality that is, at least among those embryos selected for transfer, comparable to that of embryos produced in vivo during natural cycles. In the standard IVF group: Embryo implantation = 0.11 Embryo implantation = 0.36 x embryo quality x endometrial receptivity thus Embryo quality x endometrial receptivity - 0.33 However, by design: Embryo quality (standard IVF) = Embryo quality (donor IVF) = 1 implying that Embryo receptivity (standard IVF) = 0.33 This difference in endometrial receptivity between standard IVF and donor IVF cycles implies that in stimulated cycles, endometrial receptivity is the principal limiting factor of embryo implantation lO and that as many as two thirds of transferred embryos capable of implanting fail to do so as a result of decreased endometrial receptivity. In the unstimulated IVF group: Embryo implantation = 21 % Embryo implantation = 0.36 x embryo quality x endometrial receptivity thus Embryo quality x endometrial receptivity
=
0.60
There is no clear way to assign relative value to embryo quality and endometrial receptivity in this case. However, because steroid levels and their patterns of change in these cycles are essentially natural, it seems
Embryo implantation in in vitro fertilization
Volume 163 Number 6, Part I
reasonable to assume that endometrial receptivity is uncompromised. If that is true, then Embryo quality = 0.60 Because hCG is administered in these cycles before the onset of the luteinizing hormone surge, this diminished embryo quality value may be explained as reflective of incorrect timing of hCG administration, with resultant diminished oocyte quality. Our formula and the derived approximate values for transfer efficiency, embryo quality, and endometrial receptivity are not to be taken literally. Rather, it is our intent to attempt to explain the differences in embryo implantation rates that we observed in our program and in the reports of others. We believe that the concept of transfer efficiency is an important addition to the previously introduced embryo quality and endometrial receptivity and may help to explain some of the differences in implantation rates observed under different clinical circumstances and help to define a maximal embryo implantation rate. We also tried to extrapolate from available data the approximate value of the maximal embryo implantation rate that can be expected with current techniques. We estimated this value at 36%. This number matches closely the embryo implantation rates observed in our donor oocyte IVF program. This observation led us to the conclusion that selected embryos obtained from fertilization in vitro of oocytes obtained from hyperstimulated cycles are of a quality that approximates that of in vivo fertilized embryos in natural cycles. Under the scrutiny of time and as additional data become available, the approximate values in this article will likely have to be modified. We present them as a first approximation and as a stimulus to further exploration of this topic.
2023
REFERENCES I. In vitro fertilization/ embryo transfer in the United States: 1988 results from the National IVF-ET registry. Fertil SteriI1990;53:13. 2. Walters DE, Edwards RG, Meistrich ML. A statistical evaluation of im plantation after replacing one or more human embryos. J Reprod Fertil 1985;74:557. 3. Rogers PAW, Milne BJ, Trounson AO. A model to show human uterine receptivity and embryo viability following ovarian stimulation for in vitro fertilization. J In Vitro Fert Embryo Transfer 1986;3:93. 4. Buster JE, Bustillo M, Thorneycroft IH, et al. Nonsurgical transfer of in vivo fertilized donated ova to five infertile women: report of two pregnancies. Lancet 1983;2:223. 5. Formigli L, Formigli G, Roccio C. Donation of fertilized uterine ova to infertile women. Fertil SterilI987;47:162. 6. Anderson GB. Embryo transfer in domestic animals. Adv Vet Sci Comp Med 1983;27:129. 7. Davidson A, Vermesh M, Lobo RA, Paulson RJ. Mouse embryo culture as quality control for human in vitro fertilization: the one versus two-cell model. Fertil Steri11988; 49:516. 8. Fehilly CB, CohenJ, Simons RF, Fishel SB, Edwards RG. Cryopreservation of cleaving embryos and expanded blastocysts in the human: a comparative study. Fertil Steril 1985;44:638. 9. Sauer MV, Paulson Rj, Macaso TM, Francis-Hernandez M, Lobo RA. Establishment of a nonanonymous donor oocyte program: preliminary experience at the University of Southern California. Fertil Steril 1989;52:433. 10. Paulson RJ, Sauer MV, Lobo RA. Embryo implantation following human in vitro fertilization: importance of endometrial receptivity. Fertil Steril 1990;53:870. II. Paulson RJ, Sauer MV, Francis MM, Macaso TM, Lobo RA. In vitro fertilization in unstimulated cycles [Abstract 437]. In: Proceedings of the thirty-seventh annual meeting of the Society for Gynecologic Investigation, St. Louis, March 21-24, 1990. 12. Paulson RJ, Sauer MV, Lobo RA. In vitro fertilization in unstimulated cycles: a new application. Fertil Steril 1989; 51:1059.
