Part six of the expert cycle: “Intrauterine insemination” presents the assisted reproductive technology (ART) which is intrauterine insemination. The proper qualification of a couple to the intrauterine insemination program is very important because it gives greater chances of the success of this procedure and allows to avoid both disappointments, which have huge impact on further treatment, and unnecessary costs.

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Infertility treatment with intrauterine insemination

Intrauterine insemination (IUI) is one of assisted reproductive technologies (ART). It is a simple and relatively inexpensive technique, much less invasive when compared to such procedures like IVF-ET or ICSI. Infertility treatment with artificial insemination has been known for about 200 years. It was applied for the first time by a Scottish physician, John Hunter, who placed semen of a patient with hypospadias to the vagina of his partner. But the insemination came into focus only in the course of the last several dozen years.

Besides IUI, depending on the site of semen administration, we can distinguish:

  • intracervical insemination (ICI);
  • fallopian sperm perfusion.

Still, these procedures are carried out definitely less often than intrauterine insemination.

Moreover, insemination can be divided into insemination using: partner’s sperm (IUI) and donor’s sperm (AID – artificial donor insemination).

The technique of the procedure itself, as it has been already mentioned, consists in introducing, via a flexible catheter, directly to the uterine cavity, the appropriately prepared sperm, overcoming two significant barriers – acidic vaginal pH and cervical mucus -which negatively affect both the sperm motility and number.

The procedure is carried out following pharmacological stimulation of ovulation (in induced cycle) or – uncommonly – in natural cycle.


Given numerous factors which have influence on the result of the procedure, the efficacy of one procedure with partner’s sperm is estimated as 3-10% (1). There is no evidence that two procedures carried out in the same cycle significantly affect this result.


1. Male factor:

– Lack of semen liquefaction
– Low semen parameters (10-20 million/mL, 30-50% motility of type a + b)
– Ejaculatory disorders (retrograde ejaculation)
– Hypospadias
– Sexual disorders

2. Female factor:

– Cervical factor
– Antisperm antibodies
– Stage I/II endometriosis

3. Idiopathic infertility

Abnormalities in semen analysis

The most common causes of infertility ascribable to a male partner are abnormal semen parameters. Both low sperm concentration and anomalies in their motility and morphology can be the indication for intrauterine insemination. When the ejaculate volume is too low, a solution may be two consecutive semen collections several hours apart before insemination.

It should be mentioned that attempts at treatment with gonadotropins, antiestrogens and androgens in cases of idiopathic oligozoospermia, asthenozoospermia and tetrazoospermia have not demonstrated positive effect on semen parameters, therefore IUI is often the most appropriate procedure in these situations (4).

Ejaculatory disorders

Retrograde ejaculation, a problem present in primary neurological disorders and diabetic neuropathy, as well as ejaculatory disorders with psychological background are the cause of infertility where insemination in its treatment is the method of choice.

In the situations described above, semen should be retrieved by testicular/epididymal biopsy or – in case of retrograde ejaculation – isolated from urine. Methods such as penile vibratory stimulation or transrectal electrostimulation are used to obtain semen for IUI in case of spinal cord injuries.

Cervical factor

Cervical mucus has several functions conducive to conception; among others, it separates the so-called seminal fluid from ejaculate, isolates sperm with normal motility and morphology, and has favorable effect on their survival time. The presence of cervical factor is confirmed by abnormal results of PCT (Post-Coital Test, Sims-Huhner test) which assesses, among other things, the character of cervical mucus, number, motility and vitality of the sperm present in this mucus. Many years of attempts at pharmacotherapy, including the administration of estrogens, mucolytic agents before intercourse and sodium bicarbonate irrigations, have not brought satisfactory results in the fight with cervical factor of infertility, so intrauterine insemination in combination with ovulation induction still remains the method of choice in this case.


Success of intrauterine insemination is closely related to the severity of endometriosis, and to the presence of further factors affecting the fertility of a couple.

Studies have demonstrated pregnancy rate for women with endometriosis were significantly lower (6.5%) as compared with unexplained infertility (15.3%) (7). Furthermore, the conducted studies report that the cycle fertility in case of women with mild endometriosis and in case of unaffected women is comparable, with the pregnancy rates of 22.7% and 25.7%, respectively. In turn, in women with advanced endometriosis, this rate was significantly lower (5.6%) (9). Ovulation induction significantly improves results of intrauterine insemination in women with endometriosis, while the chance for achieving pregnancy in the result of the procedure carried out in spontaneous cycle is inconsiderable (approximately 2%) (9).

Ovulation disorders

Ovarian factor in the form of ovulation disorders, both oligoovulation and anovulation, amounts to nearly 15% of infertility causes. One of the most common causes of chronic anovulation is PCOS (polycystic ovary syndrome), where the success rate of intrauterine insemination in stimulated cycle has reached approximately 20% per cycle.

Depending on applied preparations, the results are as follows: during the treatment with clomiphene or letrozole, the rate was 15-20% per cycle, while the pregnancy rate obtained after gonadotropin treatment was 20-25%, with higher risk of multifetal pregnancy in the latter group (8).

Prognostic factors

The outcome of intrauterine insemination with an infertile partner’s sperm is strongly affected by the level of abnormalities in seminogram. It has been demonstrated that definitely better results are obtained when the number of motile sperm is about 10 million (10), and that higher sperm concentration does not contribute significantly to the success of the procedure (11). Meanwhile, total sperm count below one million is associated with low likelihood of pregnancy; for this reason, in such situations resignation from intrauterine insemination will be appropriate. Further studies have demonstrated correlation between the success rate and the percentage of sperm with normal morphology. The highest efficacy of intrauterine insemination with partner sperm has been observed when the percentage of sperm with normal morphology was at least 14% (3).

The patient’s age is a constant factor affecting fertility in all couples trying for a child, therefore it isn’t without influence on the outcome of intrauterine insemination both in case of using partner or donor sperm. The highest efficacy of insemination with donor sperm is observed when a woman’s age is under 35, while in case of AID it is comparable to the pregnancy rate observed in fertile couples. In women aged over 35, the IUI success rate declines, which – if further factors are present – should prompt the decision to carry out the assessment of ovarian reserve (14).

When attempting to evaluate the effectiveness of intrauterine insemination, one cannot leave out the factors such as presence/frequency of ovulation, anatomical conditions, as well as uterine and tubal factors.

Before the procedure

The next step in the couple’s qualification for the procedure is a number of tests, including Pap smear, ultrasound examination of reproductive tract (assessing also the number of antral follicles), blood tests of both partners for sexually transmitted diseases (HCV, HIV, HBs-Ag, WR), and other tests based on individual indications (ovarian reserve evaluation, hormone level determination). Moreover, the procedure requires tubal patency assessment.

Ovarian stimulation

If a woman ovulates spontaneously and insemination is performed due to indications such as mild male factor, the procedure can be carried out in natural cycle. This should be considered also in women with high risk of ovarian hyperstimulation. But most often the first step is pharmacological ovulation induction with gonadotropins alone or in combination with clomiphene citrate and GnRH antagonists. The aim of treatment with these preparations is to obtain 1 to 3 mature follicles.

Clomiphene is a drug which is used most often. It is recommended in particular in case of patients under 37 years of age and in the third attempt at IUI if stimulation is required. It has to be stressed that clomiphene citrate used in cycles of insemination with donor sperm gives – as studies indicate – results comparable to those achieved in the natural cycle (2).

The use of gonadotropins is associated with noticeable increase in the success rate of the procedure with donor semen to 14-24% (2), but the higher rate of adverse reactions (ovarian hyperstimulation syndrome, multifetal pregnancy) demands the identification of the group of patients who require gonadotropin administration.

According to the Polish Society of Reproductive Medicine, gonadotropins (rFSH, hMG) are administered in the following cases:
– No reaction to clomiphene.
– Strong anti-estrogenic effects of clomiphene.
– Age > 37 years.

Ovulation monitoring, both in spontaneous and stimulated cycles, is necessary as the time of the procedure shows close correlation with its success; the methods which allow to calculate the periovulatory period – which is the best time for carrying out the procedure – are as follows:
1. Urine ovulation tests
2. Serum LH level measurement
3. Chorionic gonadotropin injection

Insemination is carried out 24-48 hours from the detection of LH in blood serum.

The administration of a low dose of HCG upon noticing a 17-18 mm follicle causes the end of its maturation and its rupture approximately 36 hours later, which sets the time for the performance of the procedure. We do not recommend this method, because it often causes premature, artificial maturation of the egg cell or – when administered too early – prevents physiological ovulation. At the same time, it interferes with the process of ovarian follicle forming in the next cycle.

Studies conducted in 2008, evaluating the effect of ovarian follicle rupture on the outcome of intrauterine insemination report that a ruptured follicle observed in transvaginal ultrasound examination after the procedure was related to higher pregnancy rate (over 20%) vs. the group where such follicle was not observed (ca. 8%) (6).

Semen preparation

An indispensable stage of intrauterine insemination is semen processing in laboratory settings, after semen collection from a male partner, before the insemination procedure.

Isolation has to be carried out by a laboratory diagnostician or by an embryologist. It is impermissible that the semen for insemination be prepared by a physician.

The most common methods of sperm separation from seminal fluid (seminal plasma) include: sperm washing, swim up (ascending migration technique), and density gradient centrifugation. The most important objectives of this procedure are semen changes to a large extent effected by cervical mucus, i.e. separation of sperm from seminal fluid, elimination of bacteria, isolation of sperm with normal morphology and motility.

Sperm washing consists of semen dilution, centrifugation and – in a final stage – supernatant removal. This technique allows to preserve a large number of sperm, but, due to the presence of numerous dead spermatozoa and insufficient separation of seminal plasma, it is not applied in cases where semen contains high percentage of dead or immotile sperm cells.

According to the conducted studies, sperm preparation should be carried out using swim up or density gradient centrifugation technique. These methods allow to obtain purified sperm, but the number of spermatozoa in obtained sample is significantly lower, therefore, the baseline sperm concentration in ejaculate should be taken into account. Sperm preparation does not differ from that described above in cases where the procedure is carried out with the use of frozen donor sperm. It is of no major significance whether preparation of sperm is carried out before or after its cryopreservation (5).

Insemination with donor sperm (AID)

Insemination with donor sperm is the solution in cases where the cause of the lack of children is a serious male factor of infertility and the patient rejects the treatment with in vitro fertilization, and also in cases when a man who is a carrier of genetic disorders refuses to undergo preimplantation diagnosis.

Using a sperm bank should also be considered after numerous failures of ICSI or in case of high risk of passing on the partner’s genetic disease. In such cases, the efficacy of the procedure is higher than the results obtained after insemination with partner sperm with low parameters, giving a chance for a child. Cumulative rate of pregnancies achieved through insemination with donor sperm is 9-30% (12).


Summing up, the proper qualification of a couple to the intrauterine insemination program is very important because it gives greater chances of the success of this procedure and allows to avoid both disappointments, which have huge impact on further treatment, and unnecessary costs.

The most important indications for intrauterine insemination include ejaculatory disorders, lack of or problematic semen liquefaction, hostile mucus and idiopathic infertility; however, the decision on carrying out the procedure should be taken on a case-by-case basis.

The efficacy of fallopian sperm perfusion, which raised high hopes, is not superior to IUI, therefore, with the current level of knowledge, it should not be applied on a large scale.

Complications of intrauterine insemination are rare (<1%); they include, among others, lesser pelvis infections, bleeding, reproductive organ injury, pain during the procedure as well as ovarian hyperstimulation syndrome and multiple pregnancy which are the complications of ovulation induction.

It has been demonstrated that the highest pregnancy rate is achieved during the first three cycles of intrauterine insemination and reaches approximately 30-40% in young women (13).

The number of procedures should not exceed 3-6 insemination cycles; more than one IUI in the same cycle is justified only in the absence of ovulation within 24 hours after the procedure.

Authors of the article: : Paulina Pogońska, Professor Krzysztof Łukaszuk, PhD, MD, Chief of INVICTA Fertility Clinics

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Published: 5 November 2015 Updated: 4 April 2017