Section 6
Infertility and Recurrent Pregnancy Loss
technique was found to result in pregnancy rates 2 to 3 times Male subfertility is significantly increased when the antisperm
those of intracervical insemination. However, intracervical antibody level is greater than 50%.9,10 Antisperm antibodies
insemination is still utilized in some practices.5 interfere with spermzona pellucida binding and prevent embryo
In an effort to further improve pregnancy rates, techniques cleavage and early development.
were developed to place washed sperm samples directly into the
tubes via transcerival cannulation (intratubal insemination) or Complete Evaluation
into the peritoneal cavity via a needle placed through the posterior In the presence of persistently abnormal results on semen
cul-de-sac (intraperitoneal insemination). Another technique analysis, a complete history, physical examination, and laboratory
developed in Europe, termed fallopian tube sperm perfusion, evaluation is performed to find and treat any potentially reversible
involves pressure injection of a large volume (4 mL) of washed abnormalities (see Chapter 35).
sperm sample while the cervix is sealed to prevent reflux of the
sample.6 This technique appears to have a higher pregnancy rate Female Evaluation
than IUI in couples with unexplained infertility. The remainder
of these technically difficult approaches have never been shown The female partner should undergo a basic infertility evaluation
to result in better pregnancy rates than IUI. One prospective, so that any correctable factors can be identified and treated
randomized study found that simultaneous intratubal insemination before artificial insemination (see Chapter 34). In addition to a
actually decreased the pregnancy rates associated with IUI.7 detailed history and physical examination, each woman con-
In modern clinical practice in the United States, IUI is the sidering partner or donor insemination should be evaluated with
predominant technique used for artificial insemination. an imaging technique, usually a hysterosalpingogram, to document
patent tubes. Unless oral or injectable medications are used to
induce superovulation, ovulatory function should be evaluated
EVALUATION with a urinary luteinizing hormone (LH) detection kit and mid-
luteal serum progesterone level. Further evaluation is required
Male Evaluation in the event of detection of any clinical or laboratory abnormalities.
Semen Analysis In the past, a great deal of time was spent investigating the
The male partner is initially evaluated by obtaining a complete possibility of cervical factor infertility by evaluating the character
semen analysis and screen for sperm antibodies. A minimum of and sperm survivability in periovulatory cervical mucus, using
two samples provided over 1 to 2 months is analyzed. A third what is termed a postcoital test. This test had many false-positive
sample may be required if there is a discrepancy between results, because it depended more on timing in the cycle and
the initial samples. All samples should be provided after 48 to hormonal status than on static cervical characteristics. Except
72 hours of sexual abstinence. Samples should be analyzed within for exclusion of cervicitis during pelvic examination, timed
2 hours of collection. evaluation of cervical mucus and sperm interaction is infrequently
included in a fertility examination. This is because partner IUI
Antisperm Antibodies is used as a basic fertility enhancement method for the majority
Male antisperm antibodies are found in approximately 10% of of couples who have otherwise been unable to conceive regardless
semen samples from infertile couples. Men with antisperm anti- of diagnosis.
bodies attached to their sperm are classified as having immunologic
infertility. These antibodies are believed to decrease fertility by INDICATIONS
inducing agglutination or immobilization of the sperm. Studies
have identified multiple antisperm antibodies that correspond to Partner Insemination
a variety of sperm components.
There are multiple known risk factors for the development of Partner insemination was originally developed as a treatment for
male antisperm antibodies.8 Vasectomy results in the development male factor infertility. With the advent of IUI, partner insemination
of antisperm antibodies in the majority of men. After successful has been found to be an excellent treatment for a range of diag-
vasovasostomy, more than half of these men will have detectable noses, including cervical factor infertility, unexplained infertility,
sperm-bound antibodies. The pregnancy rates will depend on and subfertility, on the basis of other diagnoses or therapeutic
many factors, including the titer and quantity of gross agglutination. measures (Table 36-2). This ability of partner insemination to
Obstructive azospermia from any cause (e.g., congenital absence increase pregnancy rates regardless of diagnosis has made this
of the vas deferens, cystic fibrosis, infant hernia repair) increases technique one of the fundamental approaches to infertility
the risk of antisperm antibodies. Reproductive infections (e.g., treatment today.
epididymitis, prostatitis, or orchitis) are also associated with
antisperm antibodies. Male Factor Infertility
Antisperm antibody tests are performed as a routine part of Partner insemination appears to be of clear benefit when the
a complete semen analysis during the initial infertility evaluation. couples infertility is the result of any condition that makes it
The most commonly used test in clinical practice is probably the difficult to place semen high in the vagina during coitus. Male
immunobead assay.8 This quantitative assay evaluates live sperm conditions resulting in this situation are termed ejaculatory failure.
and indicates percent bound, antibody isotype, and binding The most common causes of ejaculatory failure are impotence,
location. For routine screening, some andrology laboratories severe hypospadias, and retrograde ejaculation. A unique condition
use a commercially available mixed antiglobulin reaction assay that has been found to be treatable with artificial insemination
540
(SpermMar). is impotence secondary to spinal cord injury.11
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Chapter 36
Artificial Insemination
Unexplained Infertility
Unexplained (i.e., idiopathic) infertility is diagnosed after all
Partner insemination is also commonly used as a treatment known etiologies of infertility have been excluded. In these cases,
for male factor infertility documented by repeated abnormal semen analyses are normal and there is no evidence of any female
results on semen analysis. In couples where there is mild male causes of infertility, such as ovulation defects, tubal factor,
factor infertility, defined as a progressive sperm motility of at endometriosis, and cervical factor. The average incidence of
least 20% to 30%, the prognosis appears to be good with partner unexplained infertility is approximately 15% among infertile
insemination. Theoretically, increasing the number of motile couples.
sperm reaching the egg should improve fertility whenever In couples with unexplained infertility, partner IUI has been
decreased numbers and motility of normally functioning sperm demonstrated to improve pregnancy rates when used in con-
is the primary problem. junction with superovulation.13 In a meta-analysis of almost
Unfortunately, the pregnancy rates after partner IUI for the 1000 superovulation cycles for unexplained infertility, partner
treatment of severe male factor infertility have been disap- IUI was found to almost double pregnancy rates (20%) compared
pointing.12 This is probably because markedly abnormal to timed intercourse alone (11%).
parameters on routine semen analysis often reflect a sperm defect Partner IUI appears to overcome one or more unknown fertility
that decreases the ability to fertilize eggs. This type of defect is deficiencies that we cannot currently detect. Theoretically, this
unlikely to be overcome by increasing the number of sperm to might be decreased sperm transport from the vagina to the tube
which the egg is exposed at the site of fertilization. In patients secondary to either a sperm defect or an abnormality in sperm
with severely abnormal parameters on semen analysis and those transport mechanisms in the female reproductive tract. In other
with male factor infertility not amenable to partner insemination, cases, a subtle sperm fertilization defect might exist that is sur-
more effective treatment will be either donor insemination or mounted by increasing the absolute number of sperm reaching
in vitro fertilization (IVF) with intracytoplasmic sperm injection the egg.
(ICSI).
Donor Insemination
Female Factor Infertility
Female reproductive conditions can also make it difficult to In the past, the only available options for couples with severe male
place semen high in the vagina during coitus. Such conditions that factor infertility (e.g., severe oligospermia, or failure to conceive
can benefit from partner insemination include severe vaginismus using partner insemination) desiring children were either donor
and other psychological problems, and less common anatomic insemination or adoption. Since the widespread availability of
conditions. Little data exists documenting the success of partner IVF using ICSI, many couples with severe male factor infertility
insemination for these conditions. have chosen to procreate their own genetic children using these
Women with cervical factor infertility will benefit from IUI, techniques. However, donor insemination remains an option
because this approach bypasses the cervical abnormalities that when IVF/ICSI has been unsuccessful. Alternatively, many
decrease fertility. This includes women with abnormal cervical candidates for IVF/ICSI initially choose donor insemination
mucus secondary to noninfectious chronic cervicitis and women because it is less invasive and ultimately more likely to achieve
with scant mucus or cervical stenosis, usually the result of pregnancy for couples with limited resources.
cervical surgery. However, even women with a normal cervix Some women choose donor insemination because they are
and mucus appear to benefit from IUI, because the cervix not candidates for IVF/ICSI. Perhaps the most obvious situation
appears to be the limiting factor in sperm reaching the site of is women without male partners who seek pregnancy. The use
541
fertilization in the tube. of donor insemination is also indicated when the male partner
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Section 6
Infertility and Recurrent Pregnancy Loss
has no viable sperm (i.e., azoospermia) or when IVF/ICSI fails timing strategies are based on either detection of a urinary LH
to achieve fertilization. Finally, men with a known genetic surge or administration of an ultrasound-timed dose of human
disorder often choose donor insemination to avoid transmission chorionic gonadotropin (hCG ) to trigger ovulation.
to their children.
LH Surge
Donor Selection A commonly used method for timing of IUI is based on urinary
Couples choose a donor from profiles of nonidentifiable LH measurement. Ovulation occurs 40 to 45 hours after the
information. This information usually includes racial or ethnic onset of the LH surge.21 Insemination is thus planned for the
background, blood type, physical characteristics, and certain day after detection of a rise in urinary LH. This approach offers
social characteristics. Many women who become pregnant as a the simplest and most cost-effective of the indirect methods
result of donor insemination desire to use the same donor for for predicting ovulation and is just as effective in achieving
further pregnancies. pregnancy as more complex ones.22,23
Chapter 36
Artificial Insemination
Section 6
Infertility and Recurrent Pregnancy Loss
The highest pregnancy rates with IUI are seen within three to
four cycles.43 The average live birth rate per cycle is approxi-
mately 10%.18 Cumulative pregnancy rates depend on the charac-
teristics of the couples being treated. In most reports, the
cumulative pregnancy rate reaches plateau after three to six cycles.
It is difficult to predict with certainty whether pregnancy will
occur. Several models have been proposed but have not been
validated.44,45
Chapter 36
Artificial Insemination
and sperm motility was greater than 60%.50 Total motile sperm Maternal Age
count was reported to affect IUI outcome in 1115 cycles in 332 A womans age is an indirect indicator for oocyte quality, and it
infertile couples.51 No pregnancy occurred in cases where the has a significant effect on the pregnancy rates. An age-related
total motile sperm count before semen preparation was less decline in female fecundity has been documented in women
than 1 106. undergoing IUI.43,64 Successful pregnancy rates decrease after
age 35 and reduce dramatically after age 40. However, preg-
Sperm DNA Damage Tests nancies can occur at relatively advanced maternal ages, and satis-
Efforts have been made to find objective assessments of sperm factory pregnancy rates can be obtained with IUI among women
quality that will predict pregnancy outcomes in men with abnormal age 40 to 42.66,67
results on semen analysis. Three experimental assessments are
the sperm chromatin structure assay, DNA fragmentation index, Duration of Infertility
and terminal deoxynuceotidyl transferase-mediated deoxyuridine The longer the duration of infertility, the lower the pregnancy
triphosphate-nick end labeling (TUNEL). rates are after IUI.25,43,65 Although the precise limits of infertility
The sperm chromatin structure assay provides an objective duration for recommending IUI have not been clearly established,
assessment of sperm chromatin integrity and can be useful as a the pregnancy rate may be seriously compromised when infertility
fertility marker.52 In a recent study, DNA damage as measured has lasted 3 or more years.
using this test was found to predict the outcome of IUI.
The DNA fragmentation index (DFI) has been shown to be Female Fertility Factors
negatively correlated with the overall pregnancy rate in women The success of artificial insemination depends not only on the
undergoing IUI, IVF, or ICSI.53 The chances of achieving preg- quality of oocytes and spermatozoa, but also on the receptivity
nancy are significantly lower when the sperm DFI is greater than of the endometrium. In a retrospective study, the presence of
27% after IUI processing.54 uterine anomalies negatively affected the success of IUI.65
TUNEL evaluates the degree of sperm DNA fragmentation Endometrial thickness and pattern is also predictive of IUI
and stability.55 In one study, lower degrees of DNA success. In a study on women undergoing controlled ovarian
fragmentation after IUI sperm preparation correlated with hyperstimulation and IUI, a trilaminar endometrium on the day
higher pregnancy rates, and no pregnancy occurred when of IUI provided a favorable prediction of pregnancy. However,
more than 12% of sperm in an IUI specimen were TUNEL- endometrial thickness and Doppler surveys of the spiral and
positive. uterine arteries and dominant follicle gave no useful predictive
value.68 A study evaluated the role of endometrial volume
Hypo-osmotic Swelling Test measurement in predicting the pregnancy rate in women receiving
The hypo-osmotic swelling test evaluates the membrane integrity controlled ovarian hyperstimulation and IUI.69 An endometrial
of the sperm tail, detects the differences on the sperm surface, volume of less than 2 mL on three-dimensional ultrasound on
and detects subtle damage in membrane properties, which the day of insemination was associated with a poor likelihood of
reduces the ability of spermatozoa to induce a viable embryo.56 pregnancy.
A sample passes the hypo-osmotic swelling test when at least Pregnancy rates after IUI are dependent on ovum pickup and
50% of sperm in an IUI sample swell.57 Sperm specimens that transport. It follows that pregnancy rates after IUI are decreased
fail the hypo-osmotic swelling test appear to have decreased by other causes of female infertility, including tubal factor and
fertilizing ability, and thus pregnancy rates after IUI are lower. endometriosis.
The miscarriage rate was also higher when result of hypo-osmotic
swelling test was less than 50%. RISKS AND COMPLICATIONS
Section 6
Infertility and Recurrent Pregnancy Loss
a supine patient. Sitting or standing increases the risk of syncope, need to start a family, the alternatives that the male partner has
which is unlikely to occur supine. Persistent symptomatic vaso- to procreate his own genetic children, and financial factors.
vagal reactions in a supine patient will often respond to the It is recommended that the couple undergo counseling before
patient crossing her legs.70 More severe cases might require the procedure so that they can both face their feelings con-
treatment with intramuscular atropine injection (0.5 mg). cerning infertility, donor insemination, and other concerns. The
male partner may experience a loss of self-esteem and fear
Allergic Reaction losing his partner because of infertility. Both partners may feel
guilty or angry toward each other for having an infertility problem.
Allergic reactions, including anaphylaxis, can occur after IUI in
Infertility tends to separate the couple, especially when one side
response to potential allergens in the wash media. Reactions
is uncooperative. Support groups or professional counseling can
have been reported to both the bovine serum albumin and
be helpful.
antibiotics (penicillin and streptomycin) commonly used in the
wash media.71,72 Of these, penicillin allergies are the most
Offspring
common in the general population. Allergic reactions after IUI
can range from a mild skin rash to life-threatening anaphylaxis There are expert opinions both for and against disclosing to the
with laryngeal edema, bronchospasm, and hypotension. For the child that he or she is the product of donor insemination. Before
rare patient experiencing an allergic reaction after IUI, the use undergoing donor IUI, the couple should decide if they plan to
of wash media free of albumin and antibiotics is advised. disclose the nature of the procedure and the biologic impli-
cations to their friends, relatives and, ultimately, their child. If
Antisperm Antibodies knowledge of the procedure is shared with friends and relatives,
there is always the risk that the truth will be disclosed to the
When IUI was first introduced, there was a concern that the
child by someone other than the parents. These sometimes-
procedure could result in the development of serum antisperm
underappreciated issues can cause unnecessary grief if not
antibodies. Fortunately, after 40 years of experience, it appears
adequately addressed prior to therapy.
that exposure of the upper reproductive tract to washed
spermatozoa during IUI does not stimulate the appearance of
Legal Issues
clinically significant female antisperm antibodies.73
It is imperative that both partners understand the legal issues
Pregnancy-Related Complications concerning donor insemination. Before donor insemination, both
partners should sign an informed consent that clearly states the
Multiple Pregnancies
rights and obligations of the parties involved and those of the
The risk of multiple pregnancies is not increased by IUI.
child. Although laws vary from state to state, when sperm is
However, medications used to recruit multiple follicles before
obtained from a sperm bank, the donor universally has no legal
IUI do increase this risk. Clomiphene citrate is associated with
access to the couples identity. In cases where couples elect to
a twin risk of 5% to 10% and rare higher-order multiples.
use a donor known to them, an attorney should be obtained to
Injectable gonadotropins are associated with multiple pregnancy
draft the appropriate papers to terminate any parental rights of
rates of 14% to 39%.7476 Careful monitoring of the number of
the donor and give the couple full custody of any subsequent
periovulatory follicles and peak estradiol levels might decrease
child. In some states, the child conceived from donor sperm
the rate of multiple pregnancies.61,74,77 In general, women are at
may have the right to obtain identifying information about the
high risk if they are younger than age 30, have more than six
donor once they reach adulthood.
preovulatory follicles, and a peak serum estradiol level greater
than 1000 pg/mL.
PEARLS
Spontaneous Abortion and Ectopic Pregnancy
Artificial insemination is a useful and cost-effective treatment
The risk of spontaneous abortion appears to be increased after
option in selected groups of infertile couples.
IUI compared to the fertile population and is in the range of
Infertility due to cervical factor and mild male factor (without
20% to 25%.1,78 The increased risk is probably not directly
any associated female factor) can be treated with intrauterine
attributed to IUI but is most likely due to the underlying infertility
insemination without ovarian stimulation.
problem. Likewise, ectopic pregnancy rates depend largely on
Artificial insemination appears to be more cost-effective and
the presence of predisposing factors such as tubal disease and do
simple compared to the IVF/ICSI if the couples are selected
not appear to be attributed to the IUI procedure.79
appropriately.
In spite of extensive research, we are still not able to predict
PSYCHOLOGICAL, ETHICAL, AND LEGAL
the success of artificial insemination in a specific couple.
ISSUES OF DONOR INSEMINATION
Duration of the infertility negatively impacts the artificial
insemination success.
Parents
Couples with unexplained infertility have better success with
Donor insemination has more psychological implications than artificial insemination than natural intercourse.
partner insemination. Before donor insemination, several issues Couples with unexplained infertility should use controlled
should be discussed in detail, including the couples desire or ovarian hyperstimulation along with the artificial insemination.
546
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Chapter 36
Artificial Insemination
REFERENCES
1. Allen NC, Herbert CM 3rd, Maxson WS, et al: Intrauterine insemination: 23. Deaton JL, Clark RR, Pittaway DE, et al: Clomiphene citrate ovulation
A critical review. Fertil Steril 44:569580, 1985. induction in combination with a timed intrauterine insemination: The
2. Keck C, Gerber-Schafer C, Wilhelm C, et al: Intrauterine insemination value of urinary luteinizing hormone versus human chorionic gonadotropin
for treatment of male infertility. Int J Androl 20(Suppl 3):5564, 1997. timing. Fertil Steril 68:4347, 1997.
3. Cohlen BJ: Should we continue performing intrauterine inseminations 24. Van Voorhis BJ, Sparks AE, Allen BD, et al: Cost-effectiveness of
in the year 2004? Gynecol Obstet Invest 59:313, 2004. infertility treatments: A cohort study. Fertil Steril 67:830836, 1997.
4. Goverde AJ, McDonnell J, Vermeiden JP, et al: Intrauterine insemination 25. Nuojua-Huttunen S, Tomas C, Bloigu R, et al: Intrauterine insemination
or in vitro fertilisation in idiopathic subfertility and male subfertility: A treatment in subfertility: An analysis of factors affecting outcome. Hum
randomised trial and cost-effectiveness analysis. Lancet 355:1318, Reprod 14:698703, 1999.
2000. 26. Matilsky M, Geslevich Y, Ben-Ami M, et al:. Two-day IUI treatment
5. Coulson C, McLaughlin EA, Harris S, et al: Randomized controlled trial cycles are more successful than one-day IUI cycles when using
of cervical cap with intracervical reservoir versus standard intracervical frozenthawed donor sperm. J Androl 19:603607, 1998.
injection to inseminate cryopreserved donor semen. Hum Reprod 27. Ransom MX, Blotner MB, Bohrer M, et al: Does increasing frequency
11:8487, 1996. of intrauterine insemination improve pregnancy rates significantly during
6. Cantineau AE, Heineman MJ, Al-Inany H, Cohlen BJ: Intrauterine superovulation cycles? Fertil Steril 61:303307, 1994.
insemination versus Fallopian tube sperm perfusion in non-tubal sub- 28. Cohlen BJ, te Velde ER, van Kooij RJ, et al: Controlled ovarian hyper-
fertility: A systematic review based on a Cochrane Review. Hum Reprod stimulation and intrauterine insemination for treating male subfertility:
19:27212729, 2004. A controlled study. Hum Reprod 13:15531558, 1998.
7. Hurd WW, Randolph JF Jr, Ansbacher R, et al: Comparison of intra- 29. Arici A, Byrd W, Bradshaw K, et al: Evaluation of clomiphene citrate
cervical, intrauterine, and intratubal techniques for donor insemination. and human chorionic gonadotropin treatment: A prospective, randomized,
Fertil Steril 59:339342, 1993. crossover study during intrauterine insemination cycles. Fertil Steril
8. Ombelet W, Menkveld R, Kruger TF, Steeno O: Sperm morphology 61:314318, 1994.
assessment: Historical review in relation to fertility. Hum Reprod Update 30. Alborzi S, Motazedian S, Parsanezhad ME, Jannati S: Comparison of the
1:543557, 1995. effectiveness of single intrauterine insemination (IUI) versus double
9. Bronson R, Cooper G, Rosenfeld D: Sperm antibodies: Their role in IUI per cycle in infertile patients. Fertil Steril 80:595599, 2003.
infertility. Fertil Steril 42:171183, 1984. 31. Osuna C, Matorras R, Pijoan JI, Rodriguez-Escudero FJ: One versus two
10. Barratt CL, McLeod ID, Dunphy BC, Cooke ID: Prognostic value of inseminations per cycle in intrauterine insemination with sperm from
two putative sperm function tests: Hypo-osmotic swelling and bovine patients husbands: A systematic review of the literature. Fertil Steril
sperm mucus penetration test (Penetrak). Hum Reprod 7:12401244, 82:1724, 2004.
1992. 32. Alvarez JG: Nurture vs nature: How can we optimize sperm quality?
11. Ohl DA, Wolf LJ, Menge AC, et al: Electroejaculation and assisted J Androl 24:640648, 2003.
reproductive technologies in the treatment of anejaculatory infertility. 33. Saleh R, Agarwal A: Oxidative stress and male infertility: From research
Fertil Steril 76:12491255, 2001. bench to clinical practice. J Androl 23:737752, 2002.
12. Montanaro Gauci M, Kruger TF, Coetzee K, et al: Stepwise regression 34. Mortimer D: Sperm preparation methods. J Androl 21:357366,
analysis to study male and female factors impacting on pregnancy rate 2000.
in an intrauterine insemination programme. Andrologia 33:135141, 35. Rogers BJ, Perreault SD, Bentwood BJ, et al: Variability in the human
2001. hamster in vitro assay for fertility evaluation. Fertil Steril 39:204211,
13. Zeyneloglu HB, Arici A, Olive DL, Duleba AJ: Comparison of intra- 1983.
uterine insemination with timed intercourse in superovulated cycles 36. Yamamoto Y, Maenosono S, Okada H, et al: Comparisons of sperm
with gonadotropins: A meta-analysis. Fertil Steril 69:486491, 1998. quality, morphometry and function among human sperm populations
14. Sovino H, Sir-Petermann T, Devoto L: Clomiphene citrate and ovulation recovered via SpermPrep II filtration, swim-up and Percoll density
induction. Reprod Biomed Online 4:303310, 2002. gradient methods. Andrologia 29:303310, 1997.
15. Tummon IS, Asher LJ, Martin JS, Tulandi T: Randomized controlled 37. Aitken RJ, Clarkson JS: Significance of reactive oxygen species and
trial of superovulation and insemination for infertility associated with antioxidants in defining the efficacy of sperm preparation techniques.
minimal or mild endometriosis. Fertil Steril 68:812, 1997. J Androl 9:367376, 1988.
16. ASRM: New guidelines for the use of semen donor insemination: 1990. 38. Erel CT, Senturk LM, Irez T, et al: Sperm-preparation techniques for
The American Fertility Society. Fertil Steril 53:1S13S, 1990. men with normal and abnormal semen analysis. A comparison. J Reprod
17. Goldberg JM, Mascha E, Falcone T, Attaran M: Comparison of intra- Med 45:917922, 2000.
uterine and intracervical insemination with frozen donor sperm: A meta- 39. Sakkas D, Tomlinson M: Assessment of sperm competence. Semin
analysis. Fertil Steril 72:792795, 1999. Reprod Med 18:133139, 2000.
18. Rowell P, Braude P: Assisted conception. IGeneral principles. BMJ 40. Hammadeh ME, Kuhnen A, Amer AS, et al: Comparison of sperm
327:799801, 2003. preparation methods: Effect on chromatin and morphology recovery
19. Weinberg CR, Wilcox AJ: A model for estimating the potency and rates and their consequences on the clinical outcome after in vitro
survival of human gametes in vivo. Biometrics 51:405412, 1995. fertilization embryo transfer. Int J Androl 24:360368, 2001.
20. Gould JE, Overstreet JW, Hanson FW: Assessment of human sperm 41. Carrell DT, Kuneck PH, Peterson CM, et al: A randomized, prospective
function after recovery from the female reproductive tract. Biol Reprod analysis of five sperm preparation techniques before intrauterine
31:888894, 1984. insemination of husband sperm. Fertil Steril 69:122126, 1998.
21. Lenton EA, Woodward B: Natural-cycle versus stimulated-cycle IVF: Is 42. Makler A: A simple technique to increase success rate of artificial
there a role for IVF in the natural cycle? J Assist Reprod Genet insemination. Int J Gynaecol Obstet 18:1921, 1980.
10:406408, 1993. 43. Plosker SM, Jacobson W, Amato P: Predicting and optimizing success in
22. Zreik TG, Garcia-Velasco JA, Habboosh MS, et al: Prospective, an intra-uterine insemination programme. Hum Reprod 9:20142021,
randomized, crossover study to evaluate the benefit of human chorionic 1994.
gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine 44. Agarwal A, Sharma RK, Nelson DR: New semen quality scores developed
inseminations in clomiphene citrate-stimulated treatment cycles. Fertil by principal component analysis of semen characteristics. J Androl
Steril 71:10701074, 1999. 24:343352, 2003.
547
Ch36-A03309.qxd 1/23/07 5:16 PM Page 548
Section 6
Infertility and Recurrent Pregnancy Loss
45. Bedaiwy MA, Sharma RK, Alhussaini TK, et al: The use of novel semen 62. Dickey RP, Olar TT, Taylor SN, et al: Relationship of follicle number and
quality scores to predict pregnancy in couples with male-factor infertility other factors to fecundability and multiple pregnancy in clomiphene
undergoing intrauterine insemination. J Androl 24:353360, 2003. citrate-induced intrauterine insemination cycles. Fertil Steril 57:613619,
46. Hendin BN, Falcone T, Hallak J, et al: The effect of patient and semen 1992.
characteristics on live birth rates following intrauterine insemination: A 63. Mathieu C, Ecochard R, Bied V, et al: Cumulative conception rate
retrospective study. J Assist Reprod Genet 17:245252, 2000. following intrauterine artificial insemination with husbands spermatozoa:
47. Zayed F, Lenton EA, Cooke ID: Comparison between stimulated in Influence of husbands age. Hum Reprod 10:10901097, 1995.
vitro fertilization and stimulated intrauterine insemination for the 64. Tomlinson MJ, Amissah-Arthur JB, Thompson KA, et al: Prognostic
treatment of unexplained and mild male factor infertility. Hum Reprod indicators for intrauterine insemination (IUI): Statistical model for IUI
12:24082413, 1997. success. Hum Reprod 11:18921896, 1996.
48. Van Waart J, Kruger TF, Lombard CJ, Ombelet W: Predictive value of 65. Steures P, van der Steeg JW, Mol BW, et al: Prediction of an ongoing
normal sperm morphology in intrauterine insemination (IUI): A pregnancy after intrauterine insemination. Fertil Steril 82:4551, 2004.
structured literature review. Hum Reprod Update 7:495500, 2001. 66. Haebe J, Martin J, Tekepety F, et al: Success of intrauterine insemination
49. van Noord-Zaadstra BM, Looman CW, Alsbach H, et al: Delaying child- in women aged 4042 years. Fertil Steril 78:2933, 2002.
bearing: Effect of age on fecundity and outcome of pregnancy. BMJ 67. Khalil MR, Rasmussen PE, Erb K, et al: Homologous intrauterine
302:13611365, 1991. insemination. An evaluation of prognostic factors based on a review of
50. Stone BA, Vargyas JM, Ringler GE, et al: Determinants of the outcome 2473 cycles. Acta Obstet Gynecol Scand 80:7481, 2001.
of intrauterine insemination: Analysis of outcomes of 9963 consecutive 68. Tsai HD, Chang CC, Hsieh YY, et al: Artificial insemination. Role of endo-
cycles. Am J Obstet Gynecol 180:15221534, 1999. metrial thickness and pattern, of vascular impedance of the spiral and
51. Campana A, Sakkas D, Stalberg A, et al: Intrauterine insemination: uterine arteries, and of the dominant follicle. J Reprod Med 45:195200,
Evaluation of the results according to the womans age, sperm quality, 2000.
total sperm count per insemination and life table analysis. Hum Reprod 69. Zollner U, Zollner KP, Blissing S, et al: Impact of three-dimensionally
11:732736, 1996. measured endometrial volume on the pregnancy rate after intrauterine
52. Richthoff J, Spano M, Giwercman YL, et al: The impact of testicular insemination. Zentralbl Gynakol 125:136141, 2003.
and accessory sex gland function on sperm chromatin integrity as 70. Krediet CT, van Dijk N, Linzer M, et al: Management of vasovagal
assessed by the sperm chromatin structure assay (SCSA). Hum Reprod syncope: Controlling or aborting faints by leg crossing and muscle tensing.
17:31623169, 2002. Circulation 106:16841689, 2002.
53. Saleh RA, Agarwal A, Nada EA, et al: Negative effects of increased 71. Smith YR, Hurd WW, Menge AC, et al: Allergic reactions to penicillin
sperm DNA damage in relation to seminal oxidative stress in men during in vitro fertilization and intrauterine insemination. Fertil Steril
with idiopathic and male factor infertility. Fertil Steril 79(Suppl 3): 58:847849, 1992.
15971605, 2003. 72. Sonenthal KR, McKnight T, Shaughnessy MA, et al: Anaphylaxis during
54. Bungum M, Humaidan P, Spano M, et al: The predictive value of sperm intrauterine insemination secondary to bovine serum albumin. Fertil
chromatin structure assay (SCSA) parameters for the outcome of Steril 56:11881191, 1991.
intrauterine insemination, IVF and ICSI. Hum Reprod 19:14011408, 73. Moretti-Rojas I, Rojas FJ, Leisure M, et al: Intrauterine inseminations
2004. with washed human spermatozoa does not induce formation of anti-
55. Duran EH, Morshedi M, Taylor S, Oehninger S: Sperm DNA quality sperm antibodies. Fertil Steril 53:180182, 1990.
predicts intrauterine insemination outcome: A prospective cohort study. 74. Valbuena D, Simon C, Romero JL, et al: Factors responsible for multiple
Hum Reprod 17:31223128, 2002. pregnancies after ovarian stimulation and intrauterine insemination with
56. Tartagni M, Schonauer MM, Cicinelli E, et al: Usefulness of the hypo- gonadotropins. J Assist Reprod Genet 13:663668, 1996.
osmotic swelling test in predicting pregnancy rate and outcome in 75. Goldfarb JM, Peskin B, Austin C, Lisbona H: Evaluation of predictive
couples undergoing intrauterine insemination. J Androl 23:498502, factors for multiple pregnancies during gonadotropin/IUI treatment.
2002. J Assist Reprod Genet 14:8891, 1997.
57. Ombelet W, Deblaere K, Bosmans E, et al: Semen quality and intra- 76. Tur R, Buxaderas C, Martinez F, et al: Comparison of the role of cervical
uterine insemination. Reprod Biomed Online 7:485492, 2003. and intrauterine insemination techniques on the incidence of multiple
58. Ohl DA, Naz RK: Infertility due to antisperm antibodies. Urology pregnancy after artificial insemination with donor sperm. J Assist Reprod
46:591602, 1995. Genet 14:250253, 1997.
59. McLachlan RI: Basis, diagnosis and treatment of immunological infertility 77. Pasqualotto EB, Falcone T, Goldberg JM, et al: Risk factors for multiple
in men. J Reprod Immunol 57:3545, 2002. gestation in women undergoing intrauterine insemination with ovarian
60. Lombardo F, Gandini L, Dondero F, Lenzi A: Antisperm immunity in stimulation. Fertil Steril 72:613618, 1999.
natural and assisted reproduction. Hum Reprod Update 7:450456, 78. Lalich RA, Marut EL, Prins GS, Scommegna A: Life table analysis
2001. of intrauterine insemination pregnancy rates. Am J Obstet Gynecol
61. Dickey RP, Olar TT, Taylor SN, et al: Relationship of follicle number, 158:980984, 1988.
serum estradiol, and other factors to birth rate and multiparity in human 79. Aboulghar MA, Mansour RT, Serour GI: Ovarian superstimulation in
menopausal gonadotropin-induced intrauterine insemination cycles. Fertil the treatment of infertility due to peritubal and periovarian adhesions.
Steril 56:8992, 1991. Fertil Steril 51:834837, 1989.
548