Two procedures are commonly used to help couples who need fertility assistance: Through intrauterine insemination IUI , sperm is placed directly into the uterus using a speculum. Through In-vitro fertilization IVF , eggs are surgically removed using a needle that goes through the back of the vagina, and those eggs are fertilized outside of the body. IVF is usually recommended for couples facing the following situations: Severe male infertility Blocked Fallopian tubes Lack of success using IUI Concern about passing on certain genetic disorders Pre-implantation genetic testing is an advanced scientific procedure that can be performed before IVF.
Which Approach Is Best? Mary Ellen G. Pavone, MD. Rated 4. Northwestern Medical Group. A national cohort study in Denmark on singletons born after IUI showed an increased risk of adverse perinatal outcomes compared with children born after normal coitus. Stimulation with clomiphene citrate was associated with higher risk of small for gestational age compared with natural cycle IUI Malchau et al.
The reason why perinatal health problems occur more frequently after IUI is still unknown, but can be explained by the procedures itself, the endocrine changes caused by OS medication or the underlying reason for infertility Simpson, In a structured review Pinborg et al. It has been shown that spontaneous reduction of multiple pregnancies causes a higher risk for adverse obstetric and perinatal outcome compared to pregnancies without spontaneous reduction.
Survivors of a vanishing co-twin have a higher risk for prematurity and low birthweight compared to singletons from single gestations, the higher the gestational age at foetal demise, the higher the risk for the surviving co-twin Pinborg et al.
This phenomenon can explain, at least partly, the worse perinatal health outcome after OS—IUI compared to singleton and twin pregnancies born without medical assistance.
Pregnancies resulting from DI carry no increased risk compared to pregnancies obtained through normal coitus Hoy et al. The rate of birth defects was comparable to the figures reported in a general population. In addition, and not further elaborated upon here, according to the available literature, the use of frozen spermatozoa does not seem to affect the health of children. On the other hand, a clinical pregnancy resulting from IUI with donor sperm appears to increase the incidence of pre-eclampsia Kyrou et al.
No difference was observed in any risk for gestational hypertension Gonzalez-Comadran et al. Couples and single women undergoing treatment with IUI require counselling concerning the increased risk of perinatal mortality and morbidity in twins compared to singletons.
They should also be informed about an increased risk for perinatal health problems if they become pregnant after IUI with homologous and donor sperm, even for singletons, although this draft recommendation is based upon low quality evidence. A close follow-up of IUI-pregnancies from the early beginning of pregnancy is mandatory to detect spontaneous reduction of multiple pregnancies, which might be very important for that particular pregnancy.
Female age is the most relevant predictor of the probability of clinical pregnancy in IUI treatment and moderate quality evidence-based data show that a sharp decline of IUI success rate is observed in women over the age of 40 years, which is presumably related to oocyte quality Yarde and Broekmans, In heterosexual couples with unexplained infertility, IUI treatment should be limited to women with female age under 40 years, although IUI may be encouraged to continue up to 42 years when donor sperm is used Veltman-Verhulst et al.
Whether IVF or ICSI should be recommended as a first line therapy when the female is in her late 30s or above 40 years of age is still debatable and more studies are needed to examine the cost-effectiveness of such an approach Yarde and Broekmans, Male age seems to have no profound effect when the female partner or sperm recipient is younger than 35 years but a synergistic adverse effect seems to exist when the woman is older than 35 years and the man as well Mathieu et al.
A possible explanation may be a decline in sperm quality with increased male age, especially for semen volume, sperm motility and sperm morphology, but not for sperm count Kidd et al. Therefore, men in a heterosexual relationship or identified as sperm donor with a female partner above 35 years should be informed that increasing paternal age 40 years and above has a potential negative impact on IUI success rates De Brucker and Tournaye, Moreover, oxidative stress-induced mitochondrial DNA damage and nuclear DNA damage in aging men may put them at a higher risk for transmitting multiple genetic and chromosomal defects Desai et al.
Additional parameters can also influence the IUI success rates although well-organized prospective randomized trials are not available. In a structured review Ombelet et al. Their search indicated a lack of prospective studies, a lack of standardization in semen testing methodology and a huge heterogeneity of patient groups and IUI treatment strategies. The review identified an urgent need for more and better prospective cohort trials investigating the predictive value of semen parameters on IUI success rates.
The four sperm parameters most frequently examined were: inseminating motile count after washing: cut-off value between 0.
Several studies support the concept of threshold values for sperm parameters below which IUI becomes significantly less effective. When using these threshold values, a poor sensitivity for predicting pregnancy but high specificity for predicting failure to become pregnant with IUI could be observed.
Ultrasound parameters can also be used to provide important information on egg quality and endometrial receptivity that will optimize the chances of success in an IUI programme. However, robust evidence is lacking and the role of Doppler assessment in the ovaries and endometrium needs to be studied in future randomized trials Bhal et al. Endometrial thickness is another important factor predicting endometrial receptivity.
It has been shown that endometrial thickness in stimulated IUI cycles is lower than in IVF cycles and is lower in cycles stimulated with clomiphene citrate compared with natural non-stimulated cycles Randall and Templeton, Also, after a sensitivity analysis, the results remained non-significant. The authors therefore concluded that endometrial thickness is not a good prognostic factor for IUI treatment success low to moderate quality of evidence Weiss et al.
In a population-based cohort study Petersen et al. In another prospective cohort study, weight status did not influence fecundity among heterosexual couples undergoing IVF treatment Schliep et al.
However, the influence of weight on IUI outcome remains unclear. Once medication is adjusted to overcome the weight effect, the success rate is comparable for obese and normal weight women Dodson et al. In addition, an underweight BMI may also be associated with poor fertility Thijssen et al.
However, the advice to patients should be focused not only on ensuring optimal treatment outcomes, but also promoting the best obstetrical outcomes because a high BMI is undoubtedly associated with adverse obstetrical and perinatal outcome Petrozza et al.
Studies on the influence of the smoking status on IUI success rates are almost non-existent. It was shown that female smokers undergoing IUI—OS need significantly more gonadotrophins than non-smokers in order to achieve a comparable clinical pregnancy rate Farhi and Orvieto, However, focus would need to be placed on obstetrical and perinatal outcome because of the detrimental effects of smoking. IVF may become the favoured first line treatment for most causes of infertility if the singleton delivery rate per cycle can be improved through the use of SET Moolenaar et al.
Nevertheless, IUI will remain an effective first-line treatment in unexplained infertility and mild male factor infertility, as well as the use of donor sperm in same sex female couples and single women, if we succeed in increasing the delivery rate per cycle without increasing the risk for complications such as a higher MPRs and increased risk for OHSS. A well-controlled mild OS with gonadotrophins aiming for two dominant follicles is the most effective strategy when performing IUI for unexplained infertility, minimal to mild endometriosis and moderate to mild male factor infertility.
A standardized methodology for IUI taking into account evidence-based data on how to perform IUI as described in this paper will likely increase IUI singleton pregnancy rates worldwide.
Other methods to increase the delivery rate per IUI cycle will be a better selection of patients who have a reasonable prognosis with IUI.
The evidence has identified several factors that might influence IUI outcome as presented and will require further confirmation by well-designed and adequately powered randomized trials. A recent study reported a negative effect of human papilloma virus HPV positivity in women on clinical pregnancy rates following IUI Depuydt et al.
On the other hand, a reduction in medically unassisted and assisted cumulative pregnancy rates, and an increase in miscarriage rates are related to the presence of HPV sperm. The exact mechanism by which sperm infection is able to impair fertility remains unclear, and more studies are urgently needed Foresta et al. If confirmed, these results could change the clinical and diagnostic approach to infertile couples and HPV-positive women and men would, for example, not be recommended to receive IUI as a first-line treatment.
In a prospective multi-centre cohort study in France it was shown that the time interval from the end of sperm preparation to IUI in the range of 40—80 min has a potential positive effect on pregnancy rate, while not requiring the investment of supplemental resources Fauque et al. Pre-washing the catheter with culture medium prior to IUI seems to increase the success rate per cycle and could be recommended in Good Laboratory Practice Guidelines, as is already the case for embryo transfer catheters Pont et al.
In a prospective cohort study Duran et al. It is clear that more studies are needed examining the influence of certain infections, sperm DNA abnormalities and other unknown factors on IUI outcome results. More evidence-based research is also needed to optimize IUI outcome in terms of a better selection of couples or individual women who are the best candidates for IUI, therefore, these practices and appropriate strategies are not provided as additions to the draft guidelines yet.
In this article the draft recommendations on why and how to perform IUI in the forthcoming years is based on a literature search of all available evidence performed by experts invited by WHO. An exception to this is if there are circumstances where vaginal intercourse would not be appropriate or possible. After this time IVF should be offered. The data used in their calculations were not based on prospective randomized trials but derived from the published peer-reviewed literature as well as activity data of local infertility units Pashayan et al.
The methods used were criticized and according to Bahadur et al. They refer to the results of the multi-centre RCT reported by Bensdorp et al. Issues such as randomization method, allocation concealment, blinding, adequate power and outcome measures are often not dealt with adequately and thus most evidence is often graded from moderate to low.
Nevertheless, recently published higher quality multi-center RCTs fail to devalue IUI in the world of more advanced medically assisted reproductive treatments. Therefore, IUI, often in combination with OS, remains a first line treatment option for many heterosexual and same-sex infertile couples and single women as this strategy is supported by the results of cost-effectiveness trials. In the delivery of fertility care interventions and treatments, the prevention of multiple pregnancies should be as important as optimizing live birth rates.
In low and middle-income countries and settings, the prevention of infections with a high risk of transmission, including endemic viral diseases such as HIV or hepatitis, is equally important.
Finally, we presented gaps in current research, with recommendations for future research. All authors contributed to this review. All authors wrote parts of the review and reviewed the complete manuscript. Controlled ovarian hyperstimulation and intrauterine insemination for treatment of unexplained infertility should be limited to a maximum of three trials.
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The goal of ovarian stimulation with medications is to produce additional follicles so that there are more eggs available for fertilization, thereby increasing the chances of conception that month. Singletons involve much lower risk to both mother and fetus and are the goal for most doctors and fertility practices.
Most women pairing a medicated cycle with IUI will not be allowed to proceed with IUI if they are growing 4 or more follicles. Studies have shown that multi-follicular growth is associated with increased pregnancy rates in IUI with controlled ovarian hyperstimulation COH.
Be warned however that more follicles also equals a higher rate of twins, triplets, etc. Most, but not all, IUI cycles are paired with fertility medications to stimulate the follicles to produce additional eggs. What your fertility specialist recommends will be based on your medical history, diagnosis, and preferences. Using medications, the specific type, and the dosage used all affect IUI success rates. Clomid and Letrozole are both oral medications that message the brain to send stronger signals to the ovaries to ovulate, while Gonadotropin is an injectable medication that stimulates the ovaries directly to produce more follicles.
The goal is always to maximize the number of eggs hence boosting chances for conception while limiting the risk of multiple pregnancies. It is however important to note that although Clomid and Letrozole have similar odds of producing a live birth, letrozole generally has fewer side effects and more importantly, produces more singleton births.
Both fresh and frozen sperm can be used successfully with IUI. When fresh is an option, it is preferred. In part, because there is an expected loss of sperm in the thawing process, but also because timing is even more critical with washed thawed sperm.
Washed fresh sperm survive about hours, while washed thawed sperm only have a lifespan of hours. Fresh sperm tend to live a bit longer which can improve the chances of conception. One study compared pregnancy rates using fresh sperm versus cryopreserved sperm for IUI. After one cycle, pregnancy rates were higher for fresh sperm vs. Transvaginal ultrasound During a transvaginal ultrasound, your doctor or a medical technician inserts a wandlike device transducer into your vagina while you are positioned on an exam table.
Share on: Facebook Twitter. Show references Infertility FAQs. Centers for Disease Control and Prevention.
Accessed May 7, Treating infertility. American College of Obstetricians and Gynecologists. Infertility fact sheet. Ginsburg ES. Procedure for intrauterine insemination IUI using processed sperm. Intrauterine insemination IUI. Hornstein MD, et al.
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