Pregnancy outcome following fresh vs frozen embryo transfer into gestational carriers using a simplified slow freeze protocol.

PURPOSE: To compare pregnancy rates following fresh vs frozen embryo transfer into gestational carriers. METHODS: Choice of deferring fresh embryo transfer and cryopreserving the embryos vs fresh transfers was not randomized but based on circumstances. The cryopreservation protocol used a simplified slow cool technique avoiding the planar programmable freezer and using a one-step removal of the cryoprotectant. RESULTS: The live delivered pregnancy rate was 51.0% (49/96) for fresh embryo transfer vs 34.3% for transfers of frozen thawed embryos in gestational carriers not having a fresh embryo first. CONCLUSIONS: Using the simplified slow cool cryopreservation protocol with a one-step removal of cryoprotectants pregnancy rates are comparable to what is found in women of similar ages undergoing controlled ovarian hyperstimulation followed by IVF-ET. However, when transferring to a gestational carrier the live delivered pregnancy rates are 50% higher with fresh embryo transfer.

Comparison of pregnancy rates following frozen embryo transfer according to the reason for freezing: risk of ovarian hyperstimulation vs inadequate endometrial thickness.

PURPOSE: To determine the relative pregnancy rates following frozen embryo transfer according to the reason for deferring fresh embryo transfer and freezing all embryos. METHOD: A retrospective review over a 10-year time period of all in vitro fertilization (IVF) cycles that deferred fresh transfer and cryopreserved all embryos related to risk of ovarian hyperstimulation syndrome or if there was inadequate endometrial thickness. Pregnancy rates according to the reason for freezing were then compared. RESULTS: The clinical and live delivered pregnancy rates following frozen embryo transfer in women < or = age 39 was 42.8% and 31.9%, respectively for women deferring for risk of ovarian hyperstimulation syndrome vs 28.7% and 21.8% for those freezing for inadequate endometrial thickness (p = 0.01 and p = 0.07, respectively). CONCLUSION: Embryo cryopreservation may not be a complete panacea for problems of inadequate endometrial thickness.

Matched controlled study to evaluate the effect of endometrial polyps on pregnancy and implantation rates following in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To determine if endometrial polyps negatively effect outcome following in vitro fertilization-embryo transfer (IVF-ET) and whether hysteroscopic resection improves pregnancy and implantation rates and/or decreases miscarriage rates. METHODS: Retrospective study with two matched controlled groups (polyps vs no polyps) based on age and previous number of IVF failures. The polyp group was further stratified by whether polypectomy was performed or not. RESULTS: There was no difference or even trend for lower pregnancy rates or higher miscarriage rates with the presence of endometrial polyps. CONCLUSIONS: These data do not support the recommendation for hysteroscopic resection of endometrial polyps to aid conception rates.

Comparison of pregnancy outcome following frozen embryo transfer (ET) in a gestational carrier program according to source of the oocytes.

PURPOSE: To determine any differences in pregnancy rates if frozen-thawed embryos are transferred to a gestational carrier if the source of oocytes came from infertile women trying to conceive vs a paid egg donor. METHODS: Gestational carriers were used because of uterine problems or health issues. If there was adequate ovarian egg reserve, controlled ovarian hyperstimulation followed by oocyte retrieval was performed on the infertile woman. Otherwise an egg donor was used. RESULTS: No differences in clinical and ongoing delivered pregnancy rates were found but a trend for higher implantation rates in the paid donors was evident. CONCLUSIONS: The trend for higher implantation rates when a paid donor was the source of oocytes may be age-related (35.9 for infertile women vs 29.5 for paid donors). The pregnancy results with frozen embryos were sufficient to allow women to proceed with oocyte retrieval if time is of the essence even if a gestational carrier has not as yet been found.

Evaluation of the importance of late follicular phase endometrial echo patterns and pregnancy outcome following embryo transfer by evaluating infertile donor/recipient pairs.

PURPOSE: To investigate if the late follicular phase echo pattern is associated with pregnancy outcome in donors vs recipients. METHODS: Infertile donors sharing eggs with recipients were retrospectively evaluated. The endometrial echo pattern was evaluated on the day of human chorionic gonadotropin injection in donors and on the day before progesterone was given to recipients. RESULTS: Almost twice as many donors conceived when the triple-line pattern was found compared to isoechogenic (IE) (51.5% or 52/101 vs 27.3% or 6/22) but there were inadequate numbers in the IE group to show a significant difference. There was not even a trend for a difference in recipients (55.2%, 37/67 vs 53.8%, 14/26). CONCLUSIONS: The trend in this study for higher pregnancy rates in COH cycles with triple-line isoechogenic pattern in the late follicular phase will prompt a study of a larger group of patients undergoing IVF-ET in the modern era. If confirmed one treatment option would be to freeze and defer transfer to an estrogen/progesterone cycle.

Blastomere number and pregnancy rates in the succeeding in vitro fertilization cycle in women who formed all embryos with < or = 5 blastomeres.

PURPOSE: To determine the likelihood of pregnancy following the transfer of embryos all with slow cleavage to day 3. Furthermore to determine the likelihood that if slow cleavage happens once, it is likely to repeat. METHODS: A 10-year retrospective review of in vitro fertilization-embryo transfer (IVF-ET) cycles was performed to identify day 3 embryo transfers where none of the embryos had > 5 blastomeres. The pregnancy rate was then determined. If pregnancy did not occur and another IVF-ET cycle was performed it was determined what percentage of those cycles also showed 100% slow cleavage. RESULTS: The ongoing delivered pregnancy rate was 22.3% and the implantation rate was 15.6%. Of the 90 women trying another cycle 82.2% had at least one embryo with six blastomeres. The implantation rate for cycle number 2 for those with at least one 6-cell embryo was 18% (34/187) but was zero (0/17) for those not having at least a 6-cell embryo in cycle number 7. CONCLUSIONS: These data can help a couple decide whether to pursue a second cycle following an IVF-ET cycle with 100% slow cleavage embryos.

Evidence that the main adverse effect of ganirelix on pregnancy and implantation rates is on the embryo rather than the endometrium.

PURPOSE: To compare pregnancy rates following the transfer of thawed frozen embryos according to the type of GnRH antagonist or agonist used during controlled ovarian hyperstimulation (COH). METHODS: Retrospective review of frozen embryo transfers according to whether a GnRH agonist or antagonist was used. Furthermore to determine if a specific antagonist/agonist resulted in higher pregnancy rates than the other. RESULTS: The pregnancy rates in two different age categories were similar whether the COH regimen used the GnRH agonist leuprolide acetate or the GnRH antagonist cetrorelix. However, lower pregnancy rates were found with the GnRH antagonist ganirelix. CONCLUSIONS: These data reached similar conclusions as was found comparing these three agents in fresh embryo transfer.

Effect of multiple source vs single source of donor embryos on pregnancy and implantation rates per transfer.

PURPOSE: To evaluate whether using donated embryos from more than one source has a negative impact on pregnancy rates compared to a single source. METHODS: Retrospective review of all donor embryo transfers that occurred in our IVF center over a 10-year period. Embryos were all from our own patient pool. RESULTS: There were no differences in clinical or live delivered pregnancy rates. CONCLUSIONS: The willingness to choose multiple sources allows a marked reduction in the waiting time for donated embryos which are scarce. This also reduced the financial burden for couples who for religious or for ethical reasons cannot destroy the embryos and have to pay continuous embryo storage charges.

Speculum retention during embryo transfer does not improve pregnancy rates following embryo transfer--a randomized study.

PURPOSE: To corroborate or refute two previous studies that suggested that a technique using prolonged speculum retention may improve pregnancy rates per embryo transfer. METHODS: Women undergoing day 3 embryo transfer were randomly assigned to the conventional transfer technique vs the speculum retention technique. The speculum retention technique involves following the embryo transfer not to withdraw the speculum but to loosen the screw in order to exert gentle pressure on the portiovaginalis of the cervix and leave it in for seven minutes. RESULTS: Clinical and viable pregnancy rates following the standard technique were 48.9% and 44.4%, respectively, vs 43.8% and 37.5% with the speculum retention technique. The implantation rates were also similar - 37.6% vs 37.5%. CONCLUSIONS: This study was unable to corroborate the benefit of speculum retention in order to improve pregnancy rates per transfer.

A novel method to assess the effect of uterine senescence by comparing pregnancy outcome in younger donors vs older recipients who are sharing a common pool of oocytes.

PURPOSE: To evaluate uterine senescence by comparing pregnancy rates in older recipients vs their younger donors who were actually trying to conceive themselves. METHODS: A retrospective analysis comparing clinical and delivered pregnancy rates in all infertile donors < or = age 35 sharing their eggs with a recipient age > or = 40 over a 6-year time span. These parameters were also evaluated in the first frozen embryo transfer from these couples (if they had one). RESULTS: The clinical and delivered pregnancy rates were similar in younger donors vs older recipients following fresh embryo transfer. There was a non-significant trend for lower implantation rates in the younger donors. No differences were found when comparing frozen embryo transfers. CONCLUSIONS: These data support conclusions that the uterus of women > or = 40 does not inhibit embryo implantation.

The effect of endometriosis on pregnancy outcome following in vitro fertilization-embryo transfer (IVF-ET) in women with decreased egg reserve.

PURPOSE: To determine the effect of the presence of endometriosis on the delivered pregnancy rate following in vitro fertilization-embryo transfer. METHODS: A retrospective cohort analysis of fresh or frozen embryo transfer in women with diminished egg reserve having IVF-ET and who also had had a laparoscopy. The data was analyzed as to whether endometriosis was present or not. RESULTS: The data demonstrated that women with diminished egg reserve can achieve pregnancies following IVF-ET. The presence of endometriosis did not have any negative effects on pregnancy rates. CONCLUSIONS: At least in women with diminished egg reserve the presence of endometriosis did not impair outcome following IVF-ET.

Association of the change in serum estradiol (E2) levels from the day of to the day after human chorionic gonadotropin (hCG) injection and pregnancy outcome following in vitro fertilization-embryo transfer (IVF-ET) in less than average responders.

PURPOSE: To determine if the change in serum estradiol (E2) from the day of human chorionic gonadotropin (hCG) injection to the day after predicts pregnancy and implantation rates following in vitro fertilization-embryo transfer (IVF-ET) in less than average responders. METHODS: A retrospective cohort analysis was performed in women with less than average follicular response as defined by a peak serum E2 on the day of hCG of < 1500 pg/ml despite a maximum stimulation gonadotropin protocol. Pregnancy and implantation rates were compared in five groups based on standard deviation (SD) below or above the mean. RESULTS: No differences were found in outcome in any groups including those that were 1-2 SD below the mean or within 1 SD below the mean or up to 2 SD above the mean. The group that was 2 SD above the mean seemingly had higher pregnancy and implantation rates but there were insufficient numbers to allow statistical comparisons. There did not appear to be any confounding variables among these groups. CONCLUSIONS: A drop in serum E2 in a group of women that were less than average responders was not associated with a lower chance of conception following IVF-ET.

Effect of the length of time that donated embryos are frozen on pregnancy outcome.

PURPOSE: To determine if the longer length of time that embryos donated to an anonymous couple have been frozen has a negative effect of subsequent successful pregnancy following thawing and transfer to the recipients. METHODS: Retrospective determination of pregnancy rates according to the length of cryopreservation time has on pregnancy outcome following transfer of embryos designated for donation. RESULTS: Longer time of freezing did not adversely affect subsequent pregnancy rates following frozen embryo transfer. CONCLUSIONS: Donated embryos frozen for over five years (the time when some countries demand that the embryos be discarded) contributed to one-fourth of the donor embryo pool and one-third of the live deliveries.

Evidence that high serum progesterone (P) levels on day of human chorionic gonadotropin (hCG) injection have no adverse effect on the embryo itself as determined by pregnancy outcome following embryo transfer using donated eggs.

PURPOSE: To determine if too high of a level of progesterone at the time of peak follicular maturation of donors adversely affects pregnancy or implantation rates of recipients. METHODS: A retrospective cohort analysis was performed on donor egg recipients. Pregnancy rates were calculated according to ranges of five serum progesterone (P) levels based on two standard deviations before and above the mean. RESULTS: No adverse effect was found in recipients whose donors had serum P levels between 2.47 and 3.41 ng/ml. There may have been a slightly lower pregnancy rate in recipients whose donors had seen P levels over 3.41 but there were only seven patients in that group and there still was a live delivered pregnancy rate of 28.6% per transfer. CONCLUSIONS: The main adverse effect of a premature rise of progesterone in women making multiple follicles with gonadotropin stimulation seems to be on the endometrium. There appear to be enough follicles not affected by the progesterone to recommend proceeding with oocyte retrieval in the donor so as not to waste money on expensive medication and monitoring.

Increasing the dosage of progesterone (P) supplemention from the mid-luteal phase in women not attaining a mid-luteal homogeneous hyperechogenic (HH) pattern with sonography improves pregnancy rates (PRS) following frozen embryo transfer (ET).

PURPOSE: To determine if a mid-luteal phase non-homogeneous hyperechogenic (HH) endometrial echo pattern may lower pregnancy rates following frozen embryo transfer and to determine if raising the dosage of progesterone improves pregnancy outcome. METHODS: Women not attaining an HH pattern at the mid-luteal phase following estrogen-progesterone replacement were randomly given (or not) an increase in progesterone dosage. RESULTS: Increasing the progesterone dosage in those not attaining an HH pattern significantly improved the pregnancy rate relative to controls not attaining an HH pattern and showed a trend for higher pregnancy rates than those with an HH pattern. CONCLUSIONS: The mid-luteal phase echo pattern should be evaluated for a non-HH pattern so that an increase in progesterone dosage could be provided possibly resulting in higher pregnancy rates.

Artificial oocyte activation with calcium ionophore allowed fertilization and pregnancy in a couple with long-term unexplained infertility where the female partner had diminished EGG reserve and failure to fertilize oocytes despite intracytoplasmic sperm injection.

PURPOSE: To determine if fertilization and embryo development and pregnancy was possible following in vitro fertilization (IVF) in a couple with long-term unexplained infertility where the female partner had diminished egg reserve and where fertilization failure occurred despite conventional oocyte insemination and intracyoplasmic sperm injection (ICSI). METHODS: In vitro fertilization was performed using a low-dose follicle stimulating hormone (FSH) stimulation protocol. Prior to ICSI, artificial oocyte activation with calcium ionophore was used. RESULTS: Only one mature oocyte was retrieved but it fertilized and cleaved to a good quality 8-cell embryo on day 3. A pregnancy with fetal viability was achieved but she subsequently miscarried. A second attempt successful. CONCLUSIONS: Fertilization and pregnancy is possible even in women with diminished egg reserve with previous failed fertilization with ICSI by performing artificial oocyte activation with calcium ionophore. It is not clear if the sperm lacked oscillin or if the eggs were not responsive to oscillin.

The effect of cetrorelix vs. ganirelix on pregnancy outcome using minimal gonadotropin stimulation in women with elevated day 3 serum follicle stimulating hormone levels.

PURPOSE: To determine if the choice of gonadotropin releasing hormone antagonist influences subsequent pregnancy rates in women with diminished egg reserve. METHOD: Retrospective determination of pregnancy rates following embryo transfer in women with day 3 FSH >12 mIU/ml using lower dose gonadotropin stimulation regimen. RESULTS: Though no significant differences were found there was a trend for lower pregnancy rates with ganirelix vs cetrorelix. CONCLUSIONS: The trend for lower pregnancy rates with ganirelix vs. cetrorelix seen in women with diminished egg reserve is consistent with the findings of a study performed in women with normal egg reserve using a normal gonadotropin stimulation regimen. It is not clear if the adverse effect is on the endometrium or the embryo.

Successful pregnancy with frozen embryo transfer into a gestational carrier from eggs obtained from a woman in premature menopause.

PURPOSE: To describe a unique case of a successful gestational carrier pregnancy in a woman with premature ovarian failure using her own oocyte. METHODS: Despite amenorrhea, failure to have menses to progesterone withdrawal and resistance to gonadotropin stimulation, ovulation induction was attempted by restoring down-regulated follicle stimulating hormone (FSH) receptors by lowering the elevated serum FSH and allowing stimulation by endogenous or exogenous gonadotropins. Oocyte retrieval was attempted if a mature follicle was obtained. GnRH antagonist was used to prevent premature oocyte release. Tapering prednisone was used for the first five days of the cycle due to patient's history of autoimmune disease (vasculitis and Crohn's disease). IVIG was given 8/2003 for vasculitis. RESULTS: The patient underwent a total of 19 attempted retrievals during continuous natural cycles from 3/2003 to 2/2007. Oocyte retrieval required traversing the uterus with the retrieval needle because of ovarian position after multiple surgeries for bilateral endometriomas and Crohn's disease. Empty follicle syndrome was encountered in four retrieval attempts. In 15 attempts, an oocyte was obtained. The sole attempt at natural fertilization failed. ICSI and assisted hatching were used in all subsequent attempts, and were successful in all but one attempt which led to a 3 pronuclei embryo which was discarded. The first four single embryos retrieved (7, 4, 6 cells and morula) were all A1 or A2 and transferred fresh to the patient, but no pregnancy resulted. All subsequent embryos were cryopreserved. The transfer of four embryos (6-cell and 7-cell and 3-cell and 8-cell) in two cycles to two different gestational carriers resulted in a successful delivery of a full-term healthy female infant 3.3 kg. Genetic testing confirmed maternal identity to be the patient, not the carrier. CONCLUSIONS: This is the first reported case of a successful gestational carrier pregnancy after reversing ovarian failure, inducing ovulation, and transferring a frozen-thawed embryo.

The effect of length of the follicular phase on pregnancy outcome following single embryo transfer (ET) in hypergonadotropic women.

OBJECTIVE: To evaluate whether a short follicular phase adversely affects pregnancy rates following in vitro fertilization-embryo transfer in women with diminished egg reserve similarly to women with short follicular phases and normal egg reserve. METHODS: A retrospective review of women with day 3 serum FSH > 12 mIU/ml having only a single embryo transfer. Pregnancy rates were determined according to length of follicular phase, i.e., until day of egg retrieval. RESULTS: The ongoing/delivery pregnancy rates for women having oocyte retrievals on day 10 or earlier was 20.0% (20/63) compared to 16.1% (34/210) for those having retrievals on day 11 or later (p = NS). CONCLUSIONS: Either length of the follicular phase is not an important factor for achieving a pregnancy in women with diminished egg reserve or the use of ethinyl estradiol in the follicular phase negates the adverse effect of the short follicular phase even if it fails to lengthen this phase to at least ten days.

Relationship of serum progesterone (P) level the day after human chorionic gonadotropin (hCG) injection on outcome following in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To determine if either too little or too much of a rise in serum progesterone (P) on the day after human chorionic gonadotropin (hCG) injection has any negative impact on pregnancy outcome following in vitro fertilization-embryo transfer (IVF-ET). METHODS: Retrospective review. Three progesterone groups established--low, normal and high. RESULTS: There was a significantly higher clinical pregnancy rate in the normal P group vs low or high. There were no significant differences in ongoing delivered pregnancy rates but a trend for higher implantation rates in the normal P group. CONCLUSIONS: These data are consistent with the hypothesis that either too little or too much P can adversely effect implantation. However, the differences are not of sufficient magnitude to warrant a clinical intervention, e.g., deferring fresh transfer and freezing the embryos for future transfer.