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2004 ASRM Abstract

SUCCESS WITH BLASTOCYST STAGE TRANSFER IS NOT LIMITED BY MATERNAL AGE DC Merryman, KE Dalton, SE Stringfellow, VL Houserman, CA Long, and KL Honea.  ART Program of Alabama, Birmingham, AL.

Objective: Blastocyst stage transfer on day 5 of embryo culture is considered to be superior to the transfer of 8-cell embryos on day 3 of embryo culture.   The benefit to blastocyst transfer is that a lower number of blastocysts are necessary for transfer to yield a higher chance of pregnancy with a lower chance of multiple gestation.  The objective of this study was to compare the effect of maternal age on the implantation, ongoing/delivered pregnancy and multiple gestation rates during In Vitro Fertilization or Egg Recipient (IVF/ER) with blastocyst transfer.

Design: This study was designed to review the outcome of all cycles with blastocyst transfer during a three-year period, regardless of oocyte source.  Outcome was evaluated by implantation rate (IR), defined as the number of ongoing fetal heartbeats and/or live births per embryo transferred, delivery rate (ODR), defined as the number of ongoing (12 or more weeks) pregnancies and/or deliveries per transfer and high-order multiple gestation rate (HOMGR), defined as the number of ongoing and/or delivered pregnancies with triplets or more.

Materials and Methods: The data consisted of 106 blastocyst transfer cycles during the period January 2001 through January 2004.  During 2001 - 2003, cycles in which there were 6 or more embryos with 6 or more cells and ≤15% fragmentation available on day 3 of embryo culture were scheduled for blastocyst transfer.  After this period, the criteria for blastocyst transfer were extended to those cycles in which 2 embryos of good quality in excess of the number to be transferred on day 3 of embryo culture were present.  Other criteria for blastocyst transfer included: failed IVF with day 2-3 transfer, sub-optimal endometrium on day 2-3 of embryo culture and patient desire.  All cycles were included in the study and were grouped according to maternal age of oocyte source.  Stimulation and embryo culture were carried out by conventional methods.  Fisher’s exact test or Student’s t-test was used for statistical analysis as indicated.  Statistical significance was defined as P <0.05.

Results: Transfers were grouped by age <35 v. ≥35.  The IR for age <35 v. ≥35 was 33.0% v. 29.5% (P>0.05), while the ODR was 47.2% v. 52.9% (P>0.05).  The number of blastocysts transferred between groups was significantly different, 2.1 v. 2.6 (P=0.001).  The HOMGR (all triplets) was 4.8% (2/42) in the <35 age group and 11.1% (1/9) in the ≥35 age group (P>0.05).  Of note, all HOMG were the result of a three-blastocyst transfer.

Conclusion:

1)       Implantation and delivery success is not limited by maternal age ≥35 during blastocyst stage transfer.

2)       Implantation and delivery success can be optimized for maternal age ≥35 with a slight increase in the number of blastocysts transferred.

3)       The chance of high-order multiple gestation of triplets or more can be minimized by the transfer of only two blastocysts for any maternal age.

Table 1. Treatment outcome as a function of age in a group of 106 cycles with blastocyst transfer.

 

AGE

 

 

<35

≥35

P

Blastocyst transfers

89

17

-

Ongoing and/or delivered pregnancies (ODR)

42 (47.2%)

9 (52.9%)

NS

High-order multiple gestations (HOMGR)

2 (4.8%)

1 (11.1%)

NS

Blastocysts transferred (average per ET)

191 (2.1)

44 (2.6)

0.001

Ongoing fetal heart beats and/or live births (IR)

63 (33.3%)

13 (29.5%)

NS

 

DEGREE OF RE-EXPANSION OF THAWED BLASTOCYSTS IS PREDICTIVE OF FROZEN EMBRYO TRANSFER (FET) SUCCESS DC Merryman, SE Stringfellow, CA Yancey, VL Houserman, CA Long, and KL Honea.  ART Program of Alabama, Birmingham, AL.

Objective: Cryopreservation of excess embryos is routinely performed at the blastocyst stage.  The number of blastocysts to thaw for transfer during an FET cycle is sometimes difficult to assess due to the immediate appearance of the thawed blastocyst.  Frozen blastocysts contract after thawing and subsequently re-expand over time.  The objective of this study was to evaluate the quality of frozen-thawed blastocysts at two hours after thawing according to the degree of re-expansion.

Design: The current study is a retrospective analysis of the relationship of the degree of re-expansion of thawed blastocysts at two hours after thawing to ongoing pregnancy and/or delivery rate (ODR), defined as the number of ongoing pregnancies and/or deliveries per embryo transfer, and implantation rate (IR), defined as the number of ongoing fetal heartbeats and/or live births per number of embryos transferred.  Pregnancies and fetal heartbeats were considered ongoing at 12 or more weeks’ gestation.

Materials and Methods: The data consisted of 25 FET cycles in which a two-hour picture of frozen-thawed blastocysts was available.  Blastocysts were frozen and thawed utilizing glycerol and sucrose solutions.  After thawing, blastocysts were cultured for a minimum of 2 hours before transfer.  At two hours after thawing, the blastocysts were evaluated for degree of re-expansion.  Fisher’s exact test or Student’s t-test was used for statistical analysis as indicated.  Statistical significance was defined as P <0.05.

Results: FETs were grouped according to the number of blastocysts transferred with 50% or more re-expansion two hours after thawing.  An increase in ODR and IR is shown when one or more blastocysts transferred were 50% or more re-expanded two hours after thawing (see table below).  No ongoing and/or delivered pregnancies occurred when all blastocysts transferred were <50% re-expanded two hours after thawing.

Conclusion:

1)       IR and ODR can be optimized for FET cycles by evaluating the re-expansion of thawed blastocysts two hours after thawing.

2)       Thawing of excess frozen blastocysts may be avoided by initially thawing the minimum number to be transferred followed by a two hour assessment and only then thawing more if needed.

Treatment outcome as a function of blastocyst re-expansion in a group pf 25 FET cycles.

 

Number of blastocysts transferred with re-expansion to 50% or more two hours after thawing

 

0

1

2

3

4

³1

Embryo transfers

5

8

7

4

1

20

Embryos transferred (avg/ET)

13 (2.6)

16 (2.0)

17 (2.4)

14 (3.5)

4 (4.0)

51 (2.6)

Ongoing fetal heart beats and/or live births (IR)

0 (0)

3 (18.8)

1 (5.9)

5 (35.7)

1 (25.0)

10 (19.6)

Ongoing and/or delivered pregnancies (ODR)

0 (0)

3 (37.5)

1 (14.3)

3 (75.0)

1 (100)

8 (40.0)

Age (avg/ET)

31.2

30.1

31.3

30.3

34.0

30.8

 

ER SUCCESS WITH ELEVATED BODY MASS INDEX IS FACILITATED BY ADDITIONAL PROGESTERONE SUPPORT DC Merryman, CA Yancey, KE Dalton, VL Houserman, CA Long, and KL Honea.  ART Program of Alabama, Birmingham, AL.

Objective: BMI has been shown to have a negative effect on In Vitro Fertilization (IVF) and Egg Recipient (ER) success.  We previously presented data in which a body mass index (BMI) >27 resulted in a significantly lower implantation rate and ongoing/delivered pregnancy rate as compared to BMI ≤27 during IVF and ER.  The objective of this study was to evaluate the effect of additional intramuscular progesterone (IM P4) support in cycles with BMI >27 on IVF and ER success.

Design: The current study is a retrospective analysis of the outcome of all embryo transfer (ET) cycles with BMI >27.  Outcome was evaluated by ongoing pregnancy and/or delivery rate (ODR), defined as the number of ongoing pregnancies and/or deliveries per embryo transfer, and implantation rate (IR), defined as the number of ongoing fetal heartbeats and/or live births per number of embryos transferred.  Pregnancies and fetal heartbeats were considered ongoing at 12 or more weeks’ gestation.

Materials and Methods: The data consisted of 55 ETs during the period January 2002 through April 2003 (without additional IM P4) and 47 ETs during the period May 2003 through February 2004 (with additional IM P4).  Stimulation and embryo culture were carried out by conventional methods.  Fisher’s exact test or Student’s t-test was used for statistical analysis as indicated.  Statistical significance was defined as P <0.05.

Results: ETs with BMI >27 were grouped according to added IM P4 support and IVF or ER transfer.  The IR and ODR were not different with IVF when IM P4 was added.  However, the IR and ODR were significantly different with ER when IM P4 was added even though a significantly less number of embryos were transferred in this group.

Conclusion:

1)       The addition of IM P4 for ER patients with a BMI >27 resulted in a significant increase in IR and ODR.

2)       The number of embryos transferred can be maximized at two for ER success when BMI >27.

3)       The addition of IM P4 for IVF patients with a BMI >27 did not result in a significant increase in IR and ODR.

Table 1. Treatment outcome as a function of BMI in a group of 102 cycles with ET.

 

 

With Added IM P4

Without Added IM P4

 

 

P

With Added IM P4

Without Added IM P4

 

 

P

 

IVF

IVF

ER

ER

 

Embryo transfers

39

44

 

8

11

 

Embryos transferred (avg/ET)

99 (2.5)

119 (2.7)

NS

16 (2.0)

29 (2.6)

0.0001

Ongoing fetal heart beats and/or live births (IR)

13 (13.1)

14 (11.8)

NS

7 (43.8)

1 (3.4)

0.003

Ongoing and/or delivered pregnancies (ODR)

12 (30.8)

12 (27.3)

NS

5 (62.5)

1 (9.1)

0.048

 

 

2002 ASRM Abstract

Sperm Capacitation Index (SCI) predicts pregnancy outcome with Controlled Ovarian Hyperstimulation (COH) + Intrauterine Insemination (IUI). DC Merryman, SE Stringfellow, KE Dalton, VL Houserman, CA Long, and KL Honea.
ART Program of Alabama, Birmingham, AL.

Objectives: The Sperm Penetration Assay (SPA) evaluates aspects of the ability of human sperm to complete certain processes necessary to achieve fertilization using zona-free hamster oocytes. There has been controversy regarding the correlation between the SPA and fertilization of human oocytes or pregnancy outcome. An abnormal SPA is a good predictor of IVF + ICSI pregnancy outcome, but does not affect fertilization rates (Merryman, et al, ASRM poster, Orlando, FL, 2001). The SPA test produces a SCI score (average number of sperm penetrations per oocyte). Our objective was to determine the SCI score predictive of COH + IUI outcome. Clinical pregnancy per treatment cycle was used as outcome measurement.
Design: A retrospective study comparing the outcome of cycles with COH + IUI for the year 2001 in which patients had a SPA performed. SPAs were performed by Baylor College of Medicine, Houston, TX.
Materials and Methods: The data consisted of 214 COH + IUI cycles in which patients had a SPA performed. Eighty-eight cycles had a SCI =5 (“possibly impaired by” Baylor standards) while 126 cycles had a normal SCI (>5). Patients with a SCI =5 initially, may have had a repeat SPA with chymotrypsin preparation (CTP). The highest SCI obtained was used for the analysis. COH + IUI was carried out by conventional methods. If CTP improved SCI, sperm prep for IUI included CTP. Fisher exact test was used to test for differences between SCI groups.
Results: Patients were grouped according to SCI: =5 and >5. The clinical pregnancy rate (CPR) per cycle was 9% (8/88) when SCI was =5 and 20% (25/126) when SCI was >5 (P<.05). There were no clinical pregnancies in cycles with an SCI <1 (0/17). A trend towards a decrease in CPR was seen when SCI was 1-5 (8/71, 11%) vs. >5. A trend towards a decrease in CPR was noted for patients age =35 as compared to patients age <35.
Conclusions: 1) Patients with an impaired SCI of =5 have a significantly decreased clinical pregnancy rate per COH + IUI cycle as compared to patients with SCI >5. 2) Routine screening of SCI is indicated for pregnancy rate prediction for patients undergoing COH + IUI.

Sperm Capacitation Index (SCI)
0-5
>5
Total
COH/IUH Cycles
88
126
214
Clinical pregnancies
8
25
33
Clinical Pregnancy per Cycle
9%
20%(P<.05)
15%


2001 ASRM Abstract

Does In Vitro Fertilization (IVF) with Intracytoplasmic Sperm Injection (ICSI) compensate for impaired sperm function as predicted by the Sperm Penetration Assay (SPA)? DC Merryman, SE Stringfellow, CA Yancey, VL Houserman, CA Long, and KL Honea. ART Program of Alabama, Birmingham, AL.

Objectives: The SPA evaluates aspects of the ability of sperm to complete certain processes necessary to achieve fertilization using zona-free hamster oocytes. There has been controversy regarding the correlation between the ability to penetrate zona-free hamster oocytes and fertilization of human oocytes. It is unknown if the fertilization process is the only factor impaired with abnormal SPA tests. The Sperm Capacitation Index (SCI) is the number of sperm penetrations per hamster oocyte. Our objectives were 1) to determine if the SCI has a relationship with implantation rates in IVF with ICSI and 2) to determine if the SCI has a relationship with ongoing pregnancy rates in IVF with ICSI.
Design: A retrospective study comparing the outcome of IVF with ICSI from January 1998 to December 2000 in patients with an impaired SCI was performed. All SPAs were performed by Baylor College of Medicine, Houston, Texas.
Materials and Methods: The data consisted of 141 oocyte retrieval cycles in which patients had an impaired SCI. An SCI of 5 or less was considered possibly impaired. Exclusion criteria were testicular biopsy and cryobanking cycles. IVF with ICSI was carried out by conventional methods. Chi-square analysis was used to test for differences between SCI groups.
Results: Patients were grouped according to SCI: <1, 1-<4, and 4-5. The ongoing clinical pregnancy plus delivery rate (OCPD) per retrieval was 13%, 24%, and 53% respectively. Patients with an SCI of 4-5 had a significantly higher OCPD as compared to the remaining groups. The implantation rate (IR) was also significantly higher for the SCI 4-5 group as compared to the other groups. A trend towards a further reduction in OCPD and IR was noted for patients greater than age 34 with an SCI <4, as compared to patients age <35. Of note, fertilization rate with ICSI was not significantly different based on SCI result.
Conclusions: Impaired SPA is a good predictor of IVF with ICSI outcome. Patients with an impaired SCI of <4 have a significantly decreased implantation rate and significantly decreased rate of ongoing clinical pregnancy plus delivery following IVF with ICSI. Routine screening of SCI is indicated for pregnancy rate prediction for patients undergoing IVF. Future treatment for patients in whom the SPA is impaired, especially when SCI<1, may include ovulation induction with intrauterine insemination prior to IVF with ICSI or increasing the number of embryos transferred during IVF with ICSI.

SPA SCI
<1
1-<4
4-5
Oocyte retrievals (#)
53
71
17
Clinical pregnancy rate (%)
19*
28^
59*^
Implantation rate (%)
12*
18~
38*~
Delivery plus ongoing pregnancies (#)
7
17
9
Delivery plus ongoing clinical pregnancy rate per retrieval (%)
13*
24^
53*^

* = p<0.005; ~ = p<0.005; ^= p<0.05