A prospective comparison of outcome following cryopreservation using vitrification vs. a modified slow-freeze protocol of 2 pronuclear (2PN) and day 3 multi-cell embryos.

PURPOSE: To compare the efficacy of vitrification of 2 pronuclear and day 3 cleavage stage embryo vs. a modified slow freeze protocol that historically has achieved good survival and pregnancy rates at these stages. MATERIALS AND METHODS: Embryos were randomly assigned by day to freezing at the 2 proncular stage or day 3 cleavage stage embryos by either vitrification or a modified slow freeze protocol. Comparisons were made for survival rate, cleaveage rate, and pregnancy rate. RESULTS: The results were comparable with a slight edge to vitrification. Only the implantation rates of day 3 cleavage staged embryos (75% vs. 30.4%) showed a significant difference. CONCLUSIONS: Vitrification seems to be equally or possibly slightly superior to freezing embryos at the 2 pronuclear or day 3 cleavage stage vs. a modified slow freeze protocol that had been previously found to be superior to the slow freeze method of LaSalle-Testart.

Failure to increase the thickness of thin endometria with intrauterine infusion of granulocyte colony stimulating factor (G-CSF).

PURPOSE: To corroborate or refute a previous study suggesting that intrauterine infusion of granulocyte colony stimulating factor (G-CSF) could significantly improve endometrial thickness into more fertile levels when the endometrial thickness was ≤ five mm. MATERIALS AND METHODS: Three women whose endometrial thickness never exceeded five mm on the in vitro fertilization-embryo transfer (IVF-ET) cycle or subsequent attempted frozen ETs using graduated estradiol had intrauterine infusion of G-CSF to the estradiol regimen. RESULTS: Not one of the three women improved the endometrial thickness beyond five mm and none conceived on the G-CSF cycle. One woman had a subsequent pregnancy following a frozen ET with only a four-mm thickness with no infusion of G-CSF. CONCLUSIONS: These data do not confirm the efficacy of intrauterine infusion of G-CSF for poor endometrial thickness. Perhaps only certain cases will respond. A larger series could take time to accumulate since other studies have shown that only 0.3% of women with ≤ five mm endometrial thickness in the late proliferative phase during an IVF-ET cycle will not improve the endometrial thickness > five mm using graduated estradiol protocols.

Mid-luteal phase injection of subcutaneous leuprolide acetate improves live delivered pregnancy and implantation rates in younger women undergoing in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To determine if a single injection of one-mg leuprolide acetate three days after embryo transfer (ET) in younger women causes an increase in pregnancy rates, and if so, is it associated with a higher initial serum hCG level? MATERIALS AND METHODS: A prospective study was initiated where women aged ≤ 35 years were offered the option of taking the leuprolide or not. RESULTS: Though a significant difference was not found, there was a trend for higher live delivered pregnancy rates in those taking the leuprolide supplement (47.8%) vs. those not taking it (38.6%). There was no difference in the first serum beta hCG level. CONCLUSIONS: The trends is interesting enough to continue with a higher powered study.

Effect of taking a one time injection of one mg leuprolide acetate three days after embryo transfer on pregnancy outcome and level of first beta human chorionic gonadotropin (beta-hCG) level.

PURPOSE: To determine if the injection of a gonadotropin releasing hormone agonist (GnRHa) three days after embryo transfer will improve pregnancy and implantation rates. MATERIALS AND METHODS: One mg s.c. of leuprolide acetate was randomly given based on patient decision three days after embryo transfer to some patients undergoing in vitro fertilization-embryo transfer (IVF-ET). RESULTS: For women aged ≤ 43 the clinical pregnancy rate for those not taking the GnRHa was 39.5% (68/122) vs. 54.5% (42/77) for those taking leuprolide acetate (Chi-square, p = 0.0275). The respective implantation rates were 22.6% vs. 30.2% (p = 0.0495). There was no difference in first serum beta human chorionic gonadotropin (beta-hCG) levels according to whether leuprolide was used or not. CONCLUSIONS: Leuprolide acetate similar to other GnRH agonists can improve implantation rates following IVF-ET when injected once in mid-luteal phase. The beneficial effect may be on GnRH receptors in the endometrium rather than the embryo (which had been hypothesized to direct increased placental production of hCG).

The effect of oocyte reserve on pregnancy rates per oocyte harvest in women aged 36-39.

PURPOSE: To determine the relative effect of diminished oocyte reserve on clinical viable and live delivered pregnancy rates per transfer and live delivery pregnancy rate per oocyte harvest in women aged 36-39. MATERIALS AND METHODS: A retrospective comparison of pregnancy outcome was performed over a ten-year time period in women with normal oocyte reserve (day 3 serum FSH ≤ 11 mIU/mL) vs. diminished reserve (day 3 serum FSH ≥ 12 mIU/mL). Pregnancy rate per oocyte harvest equals the odds of conceiving with fresh or frozen embryos from a given retrieval before proceeding to another oocyte retrieval. RESULTS: The clinical and viable (at end of first trimester) pregnancy rate per transfer was only 20% lower for the group with diminished oocyte reserve, but was 50% lower for the pregnancy rate per oocyte harvest. CONCLUSIONS: Mild stimulation for women with diminished oocyte reserve allows a higher percentage of chromosomally normal embryos in women with diminished oocyte reserve, leading to only a 20% lower clinical and viable pregnancy rate per transfer. However, overall, there are less normal total number of normal embryos leading to a pregnancy rate per oocyte harvest only half as good in the group with lower reserve vs. normal.

The effect of conventional vs. mild ovarian hyperstimulation on the total number of live babies born from a given oocyte retrieval.

PURPOSE: To compare pregnancy outcome in women with normal oocyte reserve according to whether they received conventional or mild follicle stimulating hormone (FSH) controlled ovarian hyperstimulation (COH) further stratified by age. MATERIALS AND METHODS: A ten-year retrospective study including all cycles (even multiple in given patients) was performed. Mild stimulation including all cycles initiated and continued with 150 IU FSH or less from early follicular phase. Everything else was considered conventional stimulation. Mild stimulation included natural cycles or those with just a boost of 75 IU FSH from the mid to late follicular phase. Only women with normal oocyte reserve were selected--serum FSH < 12 mIU/mL and serum E2 < 50 pg/mL. Live delivered pregnancy rates within three age groups (≤ 35, 36-39, and 40-42 years) were compared per embryo transfer and per embryo retrieval, i.e., the percentage of women having a live baby without proceeding to another IVF-ET cycle. Also compared were the average number of babies born from one retrieval. RESULTS: For aged ≤ 35 there were no differences in pregnancy rates per transfer but a trend for higher pregnancy rates per retrieval with conventional stimulation. For all other age groups both pregnancy rates per transfer and retrieval were significantly higher with conventional stimulation. This was reflected with a higher average number of babies born per retrieval with conventional. CONCLUSIONS: For women with normal oocyte reserve in general, there is no advantage of mild vs. conventional COH other than cost saving. Of course there are exceptions, e.g., ovarian hyperstimulation with conventional COH.

Mid-luteal phase injection of subcutaneous leuprolide acetate improves live delivered pregnancy and implantation rates in younger women undergoing in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To see if the single injection of one mg of the gonadotropin releasing hormone agonist (GnRHa) leuprolide acetate given in the mid-luteal phase can increase live delivered pregnancy and implantation rates. Furthermore the purpose was to determine if improvement was found, did the mechanism involve increased secretion of human chorionic gonadotropin (hCG). MATERIALS AND METHODS: A prospective study was conducted in women aged 35 who were undergoing in vitro fertilization-embryo transfer (IVF-ET). They were advised of data from Tesarik et al. and a previous pilot study conducted in the present IVF center showing improved pregnancy rates with the injection of a GnRHa three days after embryo transfer. They were offered the option of returning for a one-mg injection s.c. of leuprolide acetate or not. Clinical and live delivered pregnancy rates were compared according to those taking or not the leuprolide acetate one-mg injection. Chi-square analysis was used for statistical comparisons. Serum beta-hCG levels were compared between those conceiving with or without the extra injection of leuprolide. RESULTS: There was a non-significant trend for higher live delivered pregnancy rates in those taking leuprolide (47.8%, 64/134) vs. those not taking it (38.6%, 76/197). For those pregnant there was no difference in hCG levels according to taking the GnRHa or not. CONCLUSIONS: The 25% increased live delivered pregnancy rate per transfer was insufficiently powered to detect a significant difference. The results do justify continuing the study. Perhaps the difference could be wider using a slightly older age group whose embryos are frequently less hearty.

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PURPOSE: To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. MATERIALS AND METHODS: Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. RESULTS: A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. CONCLUSIONS: A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

Failure to improve a thin endometrium in the late proliferative phase with uterine infusion of granulocyte-colony stimulating factor.

PURPOSE: To determine if the treatment with uterine infusion of granulocyte colony-stimulating factor (G-CSF) can improve endometrial thickness in an infertile woman with a double uterus, who consistently showed a thin endometrium in the late proliferative phase either in controlled ovarian hyperstimulation (COH) IVF-ET cycles or with graduated estrogen/sildenafil protocols for frozen embryo transfer (ET). MATERIALS AND METHODS: A single uterine infusion of G-CSF was performed in the late proliferative phase in a woman who only attained a five-mm thickness despite a high dose vaginal and oral estradiol regimen plus sildenafil. RESULTS: No increase was found within a couple days. CONCLUSIONS: A previous four-case study in another center found 100% improvement in the endometrial thickness in women with consistently thin endometria. Perhaps the uterine anomaly in the present case prevented the response of the endometrium.

A study to determine the efficacy of controlled ovarian hyperstimulation regimen using a gonadotropin releasing hormone agonist versus antagonist in women of advanced reproductive age with varying degrees of oocyte reserve on outcome following in vitro fertilization-embryo transfer.

PURPOSE: To determine if the use of gonadotropin releasing hormone (GnRH) agonists (a) or antagonists (ant) allow better pregnancy rates when used in controlled ovarian hyperstimulation protocols in women of advanced reproductive age. Furthermore the study aimed to determine if the status of ovarian oocyte reserve has a confounding effect. MATERIALS AND METHODS: A 12-year retrospective review was performed on all in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-44. Pregnancy rates were determined according to whether a GnRH-a or GnRH-ant was used. The data were also stratified according to normal or low oocyte reserve. RESULTS: There was no significant difference in pregnancy rates according to whether a GnRH-a or GnRH-ant was used in women with normal oocyte reserve. Though a large majority of the women used a GnRH-ant, there was a 9% live pregnancy rate vs 0% in the women using a GnRH-a. CONCLUSION: Since it is unlikely that a larger study will ever be conducted, it is probably wise to use a GnRH-ant for the controlled ovarian hyperstimulation regimen in women aged 40-44 with diminished oocyte reserve.

Effect of triple line vs isoechogenic endometrial texture on pregnancy outcome following embryo transfer according to use of controlled ovarian stimulation (COH) or estrogen/progesterone replacement.

PURPOSE: To determine if pregnancy rates following embryo transfer are reduced if the endometrial echo pattern in the late proliferative phase is isoechogenic (IE) vs triple line (TL). METHODS: Pregnancy and implantation rates were compared according to TL vs IE pattern in the late proliferative phase in women having in vitro fertilization-embryo transfer (IVF-ET), frozen ET, and transfer of embryos derived from donor oocytes. RESULTS: There was no difference in pregnancy rates with IE vs TL pattern with fresh or frozen ET or in donor egg recipients. The degree of ovarian reserve did not affect the pregnancy rates according to endometrial echo pattern. CONCLUSIONS: The presence of an IE pattern in the late proliferative phase should not influence the treating physician to either cancel the cycle and withhold human chorionic gonadotropin (hCG) injection or freeze all embryos and defer transfer.

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.

The sharing of eggs by infertile women who are trying to conceive themselves with an egg recipient for financial advantages does not jeopardize the donor's chance of conceiving.

PURPOSE: To determine if the sharing of oocytes by an infertile woman with an egg recipient for financial advantages has any negative impact on the success rate for the donor. METHODS: A matched controlled study was performed comparing pregnancy outcome of women undergoing in vitro fertilization-embryo transfer (IVF-ET) but sharing half of their eggs with a recipient vs women undergoing IVF-ET but not sharing oocytes. RESULTS: Even though more women sharing oocytes deferred fresh transfer and cryopreserved the embryos because of a greater likelihood of ovarian hyperstimulation syndrome, there was no difference in pregnancy rates between the two groups after their first embryo transfer whether it was with fresh or frozen-thawed embryos. CONCLUSIONS: Sharing of oocytes by a woman undergoing IVF-ET does not jeopardize her chance of a successful outcome following 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.

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.

Effect of serum progesterone level on the day of human chorionic gonadotropin injection on outcome following in vitro fertilization-embryo transfer in women using gonadotropin releasing hormone antagonists.

PURPOSE: To determine if there is any association of serum progesterone (P) level at the time of human chorionic gonadotropin (hCG) injection and pregnancy outcome in in vitro fertilization (IVF) cycles using gonadotropin releasing hormone (GnRH) antagonists for controlled ovarian hyperstimulation (COH). METHODS: A retrospective analysis of IVF cycles over a six and a half-year period where either cetrorelix or ganirelix was used with COH and at least two embryos were transferred. Female partners were < or = 35. Four different serum progesterone (P) ranges were evaluated from < or = .5 ng/ml to 1.9 ng/ml; P was measured by ELISA. RESULTS: There was no significant difference in pregnancy rates or even a trend in that direction with increasing serum P levels with either GnRH antagonist. CONCLUSIONS: At least with COH cycles using GnRH antagonists and where serum P is measured by ELISA there does not seem to be any disadvantage of higher serum P levels up to 2 ng/ml at the time of hCG in IVF-ET cycles.

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.