**[Annotated bibliography of studies in the meta-analysis]{.underline}**

**Emmet J. Lamb, 12/14/01**

1.  Subak LL, Adamson GD, Boltz NL. Therapeutic donor insemination: A
    prospective randomized trial of fresh versus frozen semen. Am J
    Obstet Gynecol 1992;166:1597-1606.

-   This is a randomized clinical trial (RCT) lasting 6 cycles.
    Randomization was by a random number table with discarding of those
    sequences with strings of 3 consecutive cycles of same treatment.
    This is the only study in which the method of randomization was
    specified. Fresh and frozen cycles used the same donor (5
    exceptions). Minimum criteria for fresh semen were total count \> 60
    million/ml (CT = 60), total motility \> 60% (MT=60), progressive
    motility \> 30% (PMT = 30).

-   There is a graph but no table of life table data. The raw data,
    however, is available to EJL. For the meta-analysis, data of table I
    was used to calculate cycle fecundity.

-   There were 15 repeat courses (72 courses in 57 women). A better
    design would be to restrict analysis to the first treatment or to
    stratify in the analysis.

2.  Iddenden DA, Sallam HN, Collins WP. A prospective randomized study
    comparing fresh semen and cryopreserved semen for artificial
    insemination by donor. Int J Fertil 1985;30:50, 55-6

-   This is a randomized clinical trial in which all cases were severe
    male factor infertility, CT \< 1 million/ml. Minimum criteria for
    fresh semen were CT = 60, MT=60, Normal morphology \> 60%. A
    constant volume of 1 ml was used for both fresh and thawed.

-   Data of Tables I and II were used to prepare a life table from which
    cycle fecundity was calculated.

3.  Keel BA, Webster BW. Semen analysis data from fresh and
    cryopreserved donor ejaculates: comparison of cryoprotectants and
    pregnancy rates. Fertil Steril 1989;52:100-5.

-   This is a randomized clinical trial with randomization at each
    cycle. Used a constant volume, 2 ml (minimum CT = 20). There were 55
    donors.

-   Data of Table 4 used to calculate cycle fecundity. No life table
    data. Used Mantel & Byer method (cites Olive D. Fertil Steril
    1986;45:157). This is appropriate when subjects transfer to other
    group after spending some time in the first group (transplantation
    after being on waiting list, adoption, medical and surgical therapy
    for endometriosis).

-   

4.  Brown CA, Boone WR, Shapiro SS. Improved cyropreserved semen
    fecundability in an alternating fresh-frozen artificial insemination
    program. Fertil Steril 1988;50:825-7

-   The first cycle was randomized and subsequent cycles alternated
    between fresh and frozen. Cross over designs in which pregnancy is
    the outcome are especially controversial.

-   Totals from Table 1 were used for estimating the cycle fecundity for
    meta-analysis. The values in Table 1 do not compute correctly for a
    life table when summed from bottom up.

5.  Richter M, Haning RV, Shapiro SS. Artificial donor insemination:
    fresh versus frozen semen; the patient as her own control. Fertil
    Steril 1984;41:277-80

-   The first cycle was randomized and subsequent cycles alternated
    between fresh and frozen. Cross over designs in which pregnancy is
    the outcome are especially controversial.

-   This is an earlier study by the same group of investigators as in
    Brown, above. The time is from 1976 to 1982 and the minimum criteria
    are less stringent: CT=60, MT=60, post thaw motility \> 50% of
    initial motility.

6.  Smith KD, Rodriguez-Rigau, Steinberger E. The influence of ovulatory
    dysfunction and timing of insemination on the success of artificial
    insemination donor (AID) with fresh or cryopreserved semen. Fertil
    Steril 1981;36:496-502.

-   We used data of Table 4 to calculate cycle fecundity.

-   Data in Table 1 does not compute correctly from bottom up.

-   Assignment to fresh or frozen was dependent on availability of fresh
    donor.

7.  Schoysman-Deboeck A, Schoysman R. Clinical comparison of fresh and
    frozen semen. Page 295-300 in David G and Price WS editors, [Human
    Artificial Insemination and Semen Preparation]{.underline}. Plenum
    Press, 1980 **AND** Schoysman-Deboeck A, Merckx M, Segal L, Vekemans
    M, Verhoeven N. Results of AID in 865 Couples, Ibid, Page 231-47.

-   Data on clinical factors listed in our table are from the second
    citation. We used data of Table 2 in the first citation to construct
    a life table limited to 12 months from which we calculated cycle
    fecundity.

-   Fresh semen was used whenever possible and frozen used if there was
    no fresh semen available.

-   Minimum criteria for fresh semen were CT = 80, MT=70. Post thaw CT
    and MT were about half that of fresh.

8.  Bordson BL, Ricci E, Dickey RP, Dunaway H, Taylor SN, Curole DN.
    Comparison of fecundability with fresh and frozen semen in
    therapeutic donor insemination. Fertil Steril 1986;46:466-9

-   We used data in Table 2, excluding cycles in which both fresh and
    frozen were employed, to calculate cycle fecundity. Numbers in Table
    1 do not compute correctly when calculated from the bottom up.

-   Minimum criteria for fresh semen were CT = 60, MT=60. For post-thaw
    CT=40, MT=30 (Motile count = 12)

9.  Jackson MCN, Richardson DW. The use of fresh and frozen semen in
    human artificial insemination. J Biosoc Sci 1977;9:251-62.

-   We used data of Table 1 to calculate cycle fecundity.

-   This study covers a 40 year period. Tubal patency was determined
    after 3-4 failed cycles.

10. Chong AP. Artificial insemination and sperm banking: clinical and
    laboratory considerations. Seminars Reprod Endocr 1985;3:193-200.

-   We used data from Tables 6 and 7 used to construct life tables for
    calculating cycle fecundity.

11. Kossoy LR, Hill GA, Herbert GM, Parker RA, Rogers BJ, Daglish CS,
    Hebert CM, Wentz AC. Luteinizing hormone and ovulation timing in a
    therapeutic donor insemination program using frozen semen. Am J
    Obstet Gynecol 1989;160:1169-72 **AND** Kossoy LR, Hill GA, Herbert
    GM, Brodie BL, Daglish CS, Dupont WD, Wentz AC. Therapeutic donor
    insemination: the impact of insemination timing with the aid of a
    urinary luteinizing hormone immunoassay. Fertil Steril 1988:49:1026.

-   This pair of papers covers the period 1984-1987 for fresh and
    1987-88 for frozen.

-   Minimum criteria for fresh semen were CT = 80, MT=60, Normal
    morphology \> 60%. For frozen semen the pre-freeze motility was
    \>70%. A hysterosalpingogram was done after 3 failed cycles and
    laparoscopy after 6.

-   We combined data from LH and BBT monitoring groups (from Table 1 of
    first paper and Table 2 of second paper) and constructed 6 cycle
    life tables from which we calculated cycle fecundity.

12. DiMarzo SJ, Huang J, Kennedy JF, Villanueva B, Hebert SA, Young PE .
    Pregnancy rates with fresh versus computer-controlled cryopreserved
    semen for artificial insemination by donor in a private practice
    setting. Am J Obstet Gynecol 1990;162:1483-90.

-   We used data of Table II to construct the life tables from which
    cycle fecundity was calculated. Cycles beyond the 10^th^ were
    omitted.

-   Fresh was used from 1970 to 1987, usually with 2 inseminations;
    frozen from 1988-90, usually with better timed single insemination.
    Women who were having inseminations at the time of the switch to
    frozen were included only in the fresh group.

-   More women using frozen were over 35 years old, 46%, than women
    using fresh, 22%.

-   Data included 153 repeat fresh treatments and 2 repeat frozen
    treatments, presumably after a pregnancy. A treatment could include
    multiple insemination cycles. A better design would be to restrict
    analysis to the first treatment or to stratify in the analysis.

13. Bartlet EM, Penney LL. Therapeutic donor insemination: fresh versus
    frozen. Missouri Medicine 1994;91:85-88.

-   We used data in Table 1 (number of cycles) and in the Results
    section text (number of pregnancies) to calculate cycle fecundity

-   Fresh semen was used in 1985-88 and frozen in 1988-91. LH monitoring
    was used predominantly in the latter period. Laparoscopy was done
    after 6 failed cycles.

-   There are duplicate treatments in both fresh (18 pregnancies among
    15 women) and frozen (32 pregnancies among 27 women). A treatment
    could include multiple insemination cycles. A better design would be
    to restrict analysis to the first treatment or to stratify in the
    analysis.

-   Table 4 cites pregnancy rates with frozen semen for 3 studies
    (Albrecht, Aiman, and Glezerman) that report only fresh semen
    results.

14. Leeton J, Selwood T, Trounson A, Wood C. Artificial donor
    insemination: frozen versus fresh semen. Aust NZ J Obstet Gynaec.
    1980;20:205

-   We used data of Table 2, combining early and late experience with
    frozen to compute cycle fecundity. Data in Table 1, life tables,
    does not compute correctly from bottom up. Authors used a modified
    life table method that did not include subjects who had withdrawn
    unless they were shown to be anovulatory in that cycle.

-   Subjects who failed to conceive after 6 cycles with frozen semen
    were given fresh semen for 1 to 3 cycles. This treatment strategy
    gives a strong bias in favor of frozen! The most fertile women
    conceive early leaving only the relatively less fertile behind after
    6 cycles to be treated with fresh semen. Despite this bias, fresh
    semen has slightly higher cycle fecundity.

15. Hammond MG, Jordon S, Sloan CS. Factors affecting pregnancy rates in
    a donor insemination program using frozen semen. Am J Obstet Gynecol
    1986;155:480-5.

-   I did not include this in the meta-analysis because it was not
    possible to obtain the needed data. Data analysis in this paper is
    especially poor and the paper is cited here only because it is
    listed in the bibliography of many papers on this subject.

-   Fresh semen was used only after 3 to 5 failed cycles of frozen.
    Fresh semen was then used when available. This treatment strategy
    gives a strong bias in favor of frozen! The most fertile women
    conceive early leaving only the relatively less fertile behind after
    6 cycles to be treated with fresh semen.

-   The comparison in Table IV is between women who had only frozen
    (cycle fecundity: 56/591 = 9.5%) and those who had both frozen and
    fresh (cycle fecundity: 47/383 = 12.3%).