Natural Cycle Intrauterine Insemination Research Articles

Intrauterine insemination timing models-LH can only take you so far.

Can an optimal LH threshold algorithm accurately predict timing of ovulation for natural cycle-intrauterine insemination (NC-IUI)? A retrospective cohort study (2018-2022) including 2467 natural cycles. Ovulation timing for these cycles was determined using a previously developed AI model. Two LH thresholds, low and high, were determined in the LH algorithm. Being below the low threshold meant that ovulation is likely to occur in ≥ 4days, suggesting another daily blood test. Between the two thresholds meant that ovulation was likely in 2-3days, suggesting IUI the next day. Above the high threshold meant that ovulation will likely occur tomorrow, suggesting performing IUI on the same day. The optimal LH model with a high threshold of 40 mIU/ml and a low threshold of 11 mIU/ml succeeded in correctly predicting timing for IUI (day - 1, - 2 relative to ovulation) in 75.4% (95%CI 75.3-75.4). In 23.1% (95%CI 23.0-23.2), the algorithm predicted "error," suggesting performing insemination when in fact it would have been performed on a non-optimal day (0 or - 3). A previously described 3-hormone-based (LH, estradiol, progesterone) AI model performed significantly better in all parameters (93.6% success rate, 4.3 "error" rate). An LH threshold model, representing common practice, evaluating all possible high and low LH threshold combinations, was successful in accurately scheduling timing for IUI in only 75% of cases. Integrating all three hormones as performed in the AI model may have an advantage in accurately predicting the optimal time for IUI, over the use of LH only.

Intrauterine Insemination After Human Chorionic Gonadotropin Trigger or Luteinizing Hormone Surge: A Meta-analysis.

To assess the odds of pregnancy after intrauterine insemination (IUI) timed by ultrasound monitoring and human chorionic gonadotropin (hCG) administration compared with monitoring luteinizing hormone (LH) levels. We searched PubMed (MEDLINE), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov (National Institutes of Health), and the Cochrane Library (Wiley) from the inception until October 1, 2022. No language limitations were applied. After deduplication, 3,607 unique citations were subjected to blinded independent review by three investigators. Thirteen studies (five retrospective cohort, four cross-sectional, two randomized controlled trials, and two randomized crossover studies) that enrolled women undergoing natural cycle, oral medication (clomid or letrozole), or both for IUI were included in the final random-effects model meta-analysis. Methodologic quality of included studies was assessed with the Downs and Black checklist. Data extraction was compiled by two authors, including publication information, hCG and LH monitoring guidelines, and pregnancy outcomes. No significant difference in odds of pregnancy between hCG administration and endogenous LH monitoring was observed (odds ratio [OR] 0.92, 95% CI 0.69-1.22, P=.53). Subgroup analysis of the five studies that included natural cycle IUI outcomes also showed no significant difference in odds of pregnancy between the two methods (OR 0.88, 95% CI 0.46-1.69, P=.61). Finally, a subgroup analysis of 10 studies that included women who underwent ovarian stimulation with oral medications (clomid or letrozole) did not demonstrate a difference in odds of pregnancy between ultrasonography with hCG trigger and LH-timed IUI (OR 0.88, 95% CI 0.66-1.16, P=.32). Statistically significant heterogeneity was noted between studies. This meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI. PROSPERO, CRD42021230520.

Is There a Relationship between Sperm DNA Fragmentation and Intra-Uterine Insemination Outcome in Couples with Unexplained or Mild Male Infertility? Results from the ID-Trial.

Sperm DNA fragmentation has been proposed as a candidate test for the assessment of sperm function on the premise that damage to the sperm chromatin is associated with a detrimental reproductive outcome. The objective of our study was to investigate whether sperm DNA fragmentation testing has a prognostic value, and thus can play a pivotal role in selecting future patients for intra-uterine insemination (IUI) therapy. This was a prospective cohort study conducted in a University Hospital setting. SDF was measured through TUNEL assay on the fresh semen sample presented at diagnosis and at insemination in couples with idiopathic/mild male infertility undergoing natural cycle IUI treatment. The generalized estimating equation (GEE)-model and multivariable model were used to analyze the probability of live birth and clinical pregnancy, respectively. ROC analysis was carried out to determine an SDF cut-off. There was an inverse relationship between SDF in the ejaculate of the diagnostic semen sample and CP (p = 0.02; OR 0.94 95% CI (0.90, 0.989)) as well as LB (p = 0.04; OR 0.95 95% CI (0.90, 0.9985)). No significant association was found between SDF after gradient and IUI outcome in the diagnostic sample nor between SDF (ejaculate/after gradient) in the IUI samples. The ROC analysis proposed a cutoff of 17.5% as the best compromise between sensitivity and specificity in the diagnostic SDF for live birth; however, the test diagnostics are low, with an AUC of 0.576. Overall, this study strengthens the hypothesis of an inverse relationship between SDF and CP/LB. Furthermore, SDF taken together with other clinical characteristics might provide more insight into male reproductive potential and predicting IUI outcome. Couples with SDF ≥ 17.5% in the diagnostic semen sample did not reach live birth. Further research is necessary to establish the diagnostic and prognostic potential of SDF as an add-on test.

P–119 The correlation between sperm chromatin fragmentation and intrauterine insemination outcome

Abstract Study question Does sperm genomic integrity affect the intrauterine insemination (IUI) outcomes in couples with unexplained infertility and young maternal age? Summary answer Spermatozoa with higher genomic integrity are correlated with higher clinical pregnancy rates in couples with unexplained infertility undergoing IUI. What is known already It is known that elevated sperm chromatin fragmentation (SCF) on the male gamete affects embryo development and implantation. This is particularly relevant in IVF as well as programmed intercourse and IUI. By complementing the standard semen analysis with an SCF assay, we can assess the competence of the male gamete and its ability to generate euploid embryos and healthy offspring. Elevated SCF has been used as a way to identify subtle male factor infertility in couples undergoing IUI with poor pregnancy outcomes in order to plan for further treatments. Study design, size, duration This is a retrospective cohort study of IUI outcomes of couples with young maternal age and a negative infertility workup treated at our center from 2016–2020. Terminal deoxynucleotidyl dUTP transferase nick-end labeling (TUNEL) assay was used to assess sperm genomic integrity. Couples were grouped based on SCF level: normal (≤15%) or abnormal (>15%). Rates of clinical pregnancy, defined as the presence of a fetal heartbeat, were compared between the groups following IUI. Participants/materials, setting, methods A total of 189 consenting couples, in which the female partner had a normal uterine cavity and patent fallopian tubes, underwent 454 IUI attempts. Only women ≤37 years old were included to control for age-related confounding factors. At least 500 spermatozoa were assessed per patient, and a threshold of ≤ 15% was considered normal. Women were either untreated for natural cycle IUI or stimulated with clomiphene citrate, gonadotropins, or Letrozole. Main results and the role of chance A total of 454 IUI cycles were reported at our center; 302 of these were carried out in 132 couples in which the male partner had normal SCF averaged at 9.29%. The average maternal age was 34.1±3 years, and the average paternal age was 37.1±5 years. These men had the following semen parameters: a concentration of 46.2±5x106/mL, 43.8±3% motility, and an average SCF of 9.3±3%. There were 45 documented clinical pregnancies (45/302, 14.9%) as confirmed by the presence of at least one fetal heartbeat detected by ultrasound; 26 delivered, 9 are ongoing, 5 were spontaneous abortions, and 5 were lost to follow-up. A total of 57 couples in which the male partner (37.2±5.9 years) had abnormal SCF underwent 152 IUI cycles (maternal age, 34.0±2.7 years). The men had the following semen parameters: an average SCF of 23.8±10 (p < 0.0001), a concentration of 26.0±10 x106/ml, and 40.1±4% motility. These IUI attempts yielded a clinical pregnancy rate of only 4.6% (7/152; P < 0.0001); 4 delivered and 3 were spontaneous abortions. Limitations, reasons for caution This study is a retrospective cohort analysis of a relatively small number of patients. Furthermore, most patients were screened for SCF due to at least one prior IUI failure. A prospective, randomized trial, in which men are concurrently screened for SCF levels at the first IUI attempt, would be ideal. Wider implications of the findings: Assessment of SCF at the initial male infertility screening can be a useful tool to investigate the competence of the male gamete. Screening couples with idiopathic infertility for a subtle male factor would guide those with higher SCF toward alternative reproductive treatments to avoid unnecessary IUI treatments. Trial registration number Not applicable

Intrauterine insemination (IUI) with or without letrozole for unexplained or mild male factor infertility: A randomized pilot study

ObjectiveTo study the feasibility of a randomized controlled trial (RCT) comparing intrauterine insemination (IUI) with and without letrozole in couples with unexplained or mild male factor infertility Study designWe performed a randomized pilot study including 100 couples with unexplained or mild male factor infertility in the Reproductive Medicine Centre of Peking University Third Hospital in China. The couples scheduled for IUI were randomized to IUI with or without ovarian stimulation (letrozole) for up to 3 cycles within a time horizon of 4 months. Women in the letrozole group received 5 mg oral letrozole daily starting from cycle day 3–5 for 5 days. Women in the natural cycle IUI group did not receive any ovarian stimulation before IUI. The primary outcome is ongoing pregnancy leading to live birth. The study was registered under trial number NCT03455426 ResultsBetween March 2018 and January 2019, 158 couples were eligible to participate after initial screening and 100 (63.3 %) couples agreed to participate. Of the 100 recruited couples, 50 were randomly allocated to IUI with letrozole and 50 to natural cycle IUI. Live birth occurred in 12 women (24.0 %) in the letrozole group and 10 women (20.0 %) in the natural cycle group (RR 1.20 (95 % CI 0.57–2.52)). Clinical pregnancy rates were 28 % and 26 % in the letrozole group and natural cycle group respectively (RR 1.08 (95 % CI 0.56–2.05). There were no multiple pregnancies in both groups. Patients were willing to be randomized and useful information was gained to plan a definitive trial. ConclusionsWe showed that an RCT comparing IUI with letrozole versus natural cycle IUI in couples with unexplained or mild male factor infertility is feasible and acceptable.

Is intrauterine insemination a viable treatment option for women over 43years old? An analysis by ovarian stimulation protocol and sperm source.

The aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation. We performed a retrospective cohort study of women 43years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed. There were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43years and over at the time of insemination (43.6 ± 0.8, range 43 to 47years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%). The use of intrauterine inseminations in women 43years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.

Natural cycle intrauterine insemination (IUI) versus ovulation induction (OI) IUI for non-infertile women

Natural cycle intrauterine insemination (IUI) versus ovulation induction (OI) IUI for non-infertile women

Ovarian stimulation in infertile women treated with the use of intrauterine insemination: a cohort study from China

To study the effectiveness of different ovarian stimulation protocols compared with natural cycle treatment in an intrauterine insemination (IUI) program. Retrospective cohort study. Large reproductive medicine center. Couples with unexplained or mild male-factor infertility. Couples were treated with the use of natural-cycle IUI, or IUI after ovarian stimulation with the use of clomiphene citrate (CC), letrozole, or gonadotropins. Live birth, multiple pregnancy rates, and cumulative live birth rates after three IUI cycles. We performed 14,519 IUI cycles in 8,583 couples. Compared with natural-cycle IUI (6.2%), live birth rates were significantly higher in IUI cycles stimulated with the use of CC (8.9%), letrozole (9.4%) and gonadotropins (9.5%). The multiple pregnancy rate resulting from natural cycles was 0.7%, compared with 4.6% in CC cycles, 1.3% in letrozole cycles, and 4.2% in gonadotropin cycles. Cumulative live birth rates after three IUI cycles were 18.4% after natural-cycle IUI, and 25.7%, 26.2%, and 23.7% with the use of CC, letrozole, and gonadotropins, respectively. In an IUI program for unexplained or mild male-factor infertility, ovarian stimulation with letrozole may significantly increase live birth rates while controlling multiple pregnancy rates.

Ovarian stimulated cycle: not a better alternative for women without ovulation disorder in intrauterine insemination.

To explore the related factors on the clinical pregnancy outcome in intrauterine insemination, a retrospective study was conducted on the clinical data of 580 cycles for 301 infertile couples who were treated with intrauterine insemination. The female age, male age, duration of infertility, treatment protocols, endometrial thickness and sperm parameters were compared between pregnant group and non-pregnant group. The results showed that there were statistical differences in female age, duration of infertility and endometrial thickness between the two groups. The pregnancy rate was 19.34% in Group A (female age ≤ 30 y) compared with 10.91% in Group B (female age > 30 y). The pregnancy rate was 18.44% when the duration of infertility ≤ 2 years, which was higher than another group 10.73% when the duration of infertility > 2 years. Group analysis according to endometrial thickness (Group1: < 8 mm; Group 2: ≥ 8 mm and ≤ 12 mm; Group 3: > 12 mm) demonstrated significant differences in clinical pregnancy rate (7.41%, 18.00% and 11.48% respectively). For those infertile female without ovulation failure, the higher clinical pregnancy rates were observed in patients undergoing intrauterine insemination in natural cycle 16.12% when compared with the patients in ovarian stimulated cycles 10.48%. Thus, we demonstrate that the pregnancy rate is related with female age, duration of infertility and endometrial thickness. The ovarian stimulated cycle couldn’t improve the pregnancy outcome for those women without ovulation disorder in intrauterine insemination.

Assisted reproductive technologies for male subfertility.

Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently used fertility treatments for couples with male subfertility. The use of these treatments has been subject of discussion. Knowledge on the effectiveness of fertility treatments for male subfertility with different grades of severity is limited. Possibly, couples are exposed to unnecessary or ineffective treatments on a large scale. To evaluate the effectiveness and safety of different fertility treatments (expectant management, timed intercourse (TI), IUI, IVF and ICSI) for couples whose subfertility appears to be due to abnormal sperm parameters. We searched for all publications that described randomised controlled trials (RCTs) of the treatment for male subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO and the National Research Register from inception to 14 April 2015, and web-based trial registers from January 1985 to April 2015. We applied no language restrictions. We checked all references in the identified trials and background papers and contacted authors to identify relevant published and unpublished data. We included RCTs comparing different treatment options for male subfertility. These were expectant management, TI (with or without ovarian hyperstimulation (OH)), IUI (with or without OH), IVF and ICSI. We included only couples with abnormal sperm parameters. Two review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the review authors. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The quality of the evidence was rated using the GRADE methods. Primary outcomes were live birth and ovarian hyperstimulation syndrome (OHSS) per couple randomised. The review included 10 RCTs (757 couples). The quality of the evidence was low or very low for all comparisons. The main limitations in the evidence were failure to describe study methods, serious imprecision and inconsistency. IUI versus TI (five RCTs)Two RCTs compared IUI with TI in natural cycles. There were no data on live birth or OHSS. We found no evidence of a difference in pregnancy rates (2 RCTs, 62 couples: odds ratio (OR) 4.57, 95% confidence interval (CI) 0.21 to 102, very low quality evidence; there were no events in one of the studies).Three RCTs compared IUI with TI both in cycles with OH. We found no evidence of a difference in live birth rates (1 RCT, 81 couples: OR 0.89, 95% CI 0.30 to 2.59; low quality evidence) or pregnancy rates (3 RCTs, 202 couples: OR 1.51, 95% CI 0.74 to 3.07; I(2) = 11%, very low quality evidence). One RCT reported data on OHSS. None of the 62 women had OHSS.One RCT compared IUI in cycles with OH with TI in natural cycles. We found no evidence of a difference in live birth rates (1 RCT, 44 couples: OR 3.14, 95% CI 0.12 to 81.35; very low quality evidence). Data on OHSS were not available. IUI in cycles with OH versus IUI in natural cycles (five RCTs)We found no evidence of a difference in live birth rates (3 RCTs, 346 couples: OR 1.34, 95% CI 0.77 to 2.33; I(2) = 0%, very low quality evidence) and pregnancy rates (4 RCTs, 399 couples: OR 1.68, 95% CI 1.00 to 2.82; I(2) = 0%, very low quality evidence). There were no data on OHSS. IVF versus IUI in natural cycles or cycles with OH (two RCTs)We found no evidence of a difference in live birth rates between IVF versus IUI in natural cycles (1 RCT, 53 couples: OR 0.77, 95% CI 0.25 to 2.35; low quality evidence) or IVF versus IUI in cycles with OH (2 RCTs, 86 couples: OR 1.03, 95% CI 0.43 to 2.45; I(2) = 0%, very low quality evidence). One RCT reported data on OHSS. None of the women had OHSS.Overall, we found no evidence of a difference between any of the groups in rates of live birth, pregnancy or adverse events (multiple pregnancy, miscarriage). However, most of the evidence was very low quality.There were no studies on IUI in natural cycles versus TI in stimulated cycles, IVF versus TI, ICSI versus TI, ICSI versus IUI (with OH) or ICSI versus IVF. We found insufficient evidence to determine whether there was any difference in safety and effectiveness between different treatments for male subfertility. More research is needed.

Intra-uterine insemination for unexplained subfertility.

Background Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates. Objectives To determine whether for couples with unexplained subfertility IUI improves the live birth rate compared with timed intercourse (TI), both with and without ovarian hyperstimulation. Search strategy We searched the Cochrane Menstrual Disorder and Subfertility Group Trials Register ( searched March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), SCIsearch and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. Selection criteria Truly randomised controlled trials (RCTs) with at least one of the following comparisons were included: - IUI versus TI, both in a natural cycle; - IUI versus TI, both in a stimulated cycle; - IUI in a natural cycle versus IUI in a stimulated cycle; - IUI with OH versus TI in natural cycle; - IUI in a natural cycle versus TI with OH. Only couples with unexplained subfertility were included. Data collection and analysis Quality assessment and data extraction were performed independently by two review authors. Outcomes were extracted and the data were pooled. Subgroup analyses and sensitivity analyses were done where possible. Main results In the six trials where IUI was compared with TI, both in stimulated cycles, there was evidence of an increased chance of pregnancy (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50). A significant increase in pregnancy rate was also found for women where IUI with OH was compared with IUI in a natural cycle (three RCTs, 415 women: OR 2.33, 95% CI 1.46 to 3.71). However, the trials provided insufficient data to investigate the impact of IUI with or without OH on several important outcomes including live birth, multiple pregnancies, miscarriage and risk of ovarian hyperstimulation. There was no evidence of a difference in pregnancy rate for IUI with OH compared with TI in a natural cycle (one RCT, 51 women: OR 4.05, 95% CI 0.39 to 41.87). No RCTs were found for the other two comparisons. Authors' conclusions There is evidence that IUI with OH increases the live birth rate compared to IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared to TI both in stimulated cycles. There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. Therefore, couples should be fully informed about the risks of IUI and OH as well as alternative treatment options.

PIH89 - Evaluation of Patient and Financial Outcomes Associated With Advanced Infertility Treatment Options

A model was designed to evaluate infertility treatment protocols and examines the medical and pharmacy budget impact from a patient and health plan perspective. An Excel-based platform (Microsoft Excel 2010) was designed to model the cost and expected number of pregnancies associated with the following advanced infertility treatments: natural cycle intrauterine insemination (IUI), IUI with clomiphene citrate (IUI-C), IUI with gonadotropins (IUI-G), in vitro fertilization (IVF) and IVF with intracytoplasmic injection (IVF+ICSI). The model is designed to customize inputs within key parameters including population, treatment strategies and health plan coverage. Standard fertility treatment strategy can choose to enter one of five standard first line treatment pathways including IUI, IUI-C, IUI-G, IVF or IVF+ICSI. Fast track fertility treatment strategy does not include the use of IUI-G. Health plan coverage allows end user to input drug coverage (yes/no, copayment per cycle and patient coinsurance) and procedure coverage (yes/no, number of cycles covered, copayment, number of covered doctor visits per cycle and patient coinsurance). Default model population of women initiating fertility treatment is 1,555. The total cost to the health plan per year (health plan perspective) for the standard fertility treatment strategy is about 50M USD compared to the fast track fertility treatment strategy at about 41M USD for a net budget impact of 9M USD. The average cost per patient per year (patient perspective) for the standard fertility treatment strategy is approximately 4,800 USD compared to the fast track fertility treatment strategy at an estimated 4,200 USD for a net budget impact of approximately 600 USD. Results vary upon user inputs. An Excel-based model was developed to assist managed care organizations and employers with the development of an optimal fertility benefit design. The model serves as an educational tool to evaluate various fertility benefit designs in terms of patient and financial outcomes.

Perinatal outcomes in 6,338 singletons born after intrauterine insemination in Denmark, 2007 to 2012: the influence of ovarian stimulation

To study perinatal outcomes in singletons born after intrauterine insemination (IUI) compared with children born after invitro fertilization (IVF), intracytoplasmic sperm injection, and spontaneous conception (SC), and to assess predictors of poor outcome in singletons born after IUI, exploring the effect of ovarian stimulation. National cohort study, 2007-2012. Danish national registries. Four thousand two hundred twenty-eight singletons born after insemination with partner semen (IUI-H) and 1,881 singletons born after insemination with donor semen. None. Preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA). Children born after IUI-H had higher risks of PTB, LBW, and SGA vs. SC singletons (adjusted odds ratios [aOR] 1.3; 95% confidence interval (CI), 1.1-1.5; 1.4; 95% CI, 1.2-1.7; and 1.4; 95% CI, 1.2-1.6), respectively. Compared with IVF, risk of SGA was similar, but risks of PTB and LBW were lower (aOR 0.6; 95% CI, 0.5-0.8; and 0.8; 95% CI, 0.6-0.9). Compared with intracytoplasmic sperm injection, no differences were found. For children born after IUI with donor semen, results were similar to those for IUI-H. Risks of LBW and SGA were higher in IUI singletons born after ovarian stimulation with clomiphene citrate, compared with natural-cycle IUI (aOR 1.5; 95% CI, 1.1-2.1 and 1.6; 95% CI, 1.1-2.4). Treatment with follicle-stimulating hormone vs. natural-cycle IUI did not seem to affect perinatal outcomes. Singletons born after IUI had higher risk of adverse perinatal outcomes compared with SC children, similar to ICSI, but favorable outcomes compared with IVF. Stimulation with clomiphene citrate was associated with higher risk of SGA compared with natural-cycle IUI, but follicle-stimulating hormone treatment did not seem to be associated with adverse outcomes.

Spontaneous triggering of ovulation versus HCG administration in patients undergoing IUI: a prospective randomized study

The objective of this prospective randomized study was to assess whether spontaneous triggering of ovulation by detecting LH rise with serial serum testing, results in higher pregnancy rates as compared with administration of human chorionic gonadotrophin (HCG) in patients undergoing intrauterine insemination (IUI) in natural cycles. The trial was registered in clinicaltrials.gov as NCT01414673. Three hundred patients treated by IUI in natural cycles at the Centre of Reproductive Medicine of the Dutch-Speaking Brussels Free University were randomized to either spontaneous triggering of ovulation (spontaneous LH group) (n=150) or administration of HCG (n=150). Donor spermatozoa was used in 197/300 patients (65.67%). The duration of the follicular phase was significantly higher in the spontaneous LH group as compared with the HCG group (P=0.004). However, the ongoing pregnancy rate was significantly higher in the spontaneous LH group as compared with the HCG group (34/150 versus 16/150, P=0.008; difference 12.0%, 95% CI – 3.6 to 20.4). The use of LH for timing ovulation in natural cycles might be the best way to maximize the probability of pregnancy for patients undergoing IUI.It remains unclear whether the probability of pregnancy is associated with the mode of ovulation triggering in intrauterine insemination (IUI) natural cycles. The aim of this study was to assess prospectively whether spontaneous triggering of ovulation by detecting LH rise results in higher pregnancy rates as compared to administration of human chorionic gonadotrophin (HCG) in patients undergoing IUI. Based on our results, spontaneous triggering of ovulation is associated with significantly higher ongoing pregnancy rates compared with administration of HCG in patients undergoing IUI. Therefore, the use of LH for timing ovulation in natural cycles might be the best way to maximize the probability of pregnancy for patients undergoing IUI.

Investigation of Whether a Follicular Assessment using Ultrasonography and Serum Estradiol Measurements Can Improve the Pregnancy Rate of a Natural Menstrual Cycle Intrauterine Insemination

The aim of this study is to investigate whether a natural cycle intrauterine insemination (NC-IUI) monitored with ultrasonography and serum estradiol level can improve the pregnancy rate (PR) of NC-IUI. A total of 311 cycles of 135 cases was treated with a NC-IUI using a ultrasonographic monitor for follicular development (Group A). And a total of 308 cycles of 131 cases underwent a NC-IUI monitored baseline ovarian cysts, follicular development and ovulation using ultrasonography and serum estradiol level (Group B). Forty-two cycles (12.0%) were cancelled due to baseline ovarian cysts and 20 cycles (6.1%) were excluded from group B because of a luteinized unruptured follicle. In group A and B, 16 pregnancies (5.1% per cycle) and 32 pregnancies (10.4% per cycle) were obtained respectively. The differences between the PRs of the two groups attained statistical significance (P < 0.05). Our data indicated that a NC-IUI monitored with ultrasonography and serum estradiol level may improve the PR of NC-IUI.

Intrauterine insemination in natural cycle may give better results in older women

Controlled ovarian hyper-stimulation (COH) in combination with intrauterine insemination (IUI) has been shown to result in significantly higher pregnancy rates compared to un-stimulated (natural cycle) IUI. This may however not be true in all ages. We performed a retrospective cohort study and analysed data collected prospectively on 1759 IUI cycles in couples with unexplained infertility. The results were analysed to show the outcome of IUI with COH, and IUI in natural cycle (unstimulated), in younger women compared to their older counterparts. In women age 37 and younger, COH resulted in a significantly higher pregnancy rate (13.0% vs 6.5%) and live-birth rate (10.7% vs 5.2%) compared to natural cycle IUI (p = 0.025, p = 0.045 respectively). However for older women age >37 years, natural cycle (unstimulated) IUI, resulted in a significantly higher pregnancy rate (12.0% vs 8.5%) live-birth rate (7.5%vs 3.5%) than IUI with COH ((p = 0.0037). This difference is even more significant when COH was performed with clomiphene citrate (7.5% vs 2.1%) (p = 0.0017). COH was associated with a lower live birth rate in older women, irrespective of the agent used, and it seems to be worse when the anti-oestrogenic drug clomiphene citrate was used for COH. Older women may benefit more from natural cycle (unstimulated) IUI. A randomised controlled trial is required to confirm this observation.

Intrauterine insemination: facts and fairy-tales

This review tries to separate the fairy-tales from the facts regarding intrauterine insemination as treatment option for subfertile couples. Intrauterine insemination in natural cycles has been proven effective for male subfertility and cervical hostility. In case of unexplained or mild male subfertility IUI should be applied in cycles with mild ovarian hyperstimulation. Concern exists regarding the achievement of multiple pregnancies after MOH/IUI. With adequate treatment strategies the number of multiple pregnancies can be reduced to acceptable numbers. Intrauterine insemination is a cost-effective treatment option for most of our subfertile couples and should therefore be offered as a first-line treatment option. Government decisions should not interfere with good clinical practice.

Timed intercourse versus intra-uterine insemination with or without ovarian hyperstimulation for subfertility in men.

Although intra-uterine insemination (IUI) is widely used, however its effectiveness remains a matter of debate. Although IUI is less invasive and expensive than IVF or GIFT, it should only be applied if the probability of conception is improved significantly as compared to the natural chance of conceiving. To increase the number of available oocytes at the site of fertilization, controlled ovarian hyperstimulation (COH) can be applied in conjunction with IUI. Uncontrolled studies suggest a beneficial effect of COH in combination with IUI, also when a male factor is present. To be able to draw firm conclusions whether IUI and/or COH improve the probability of conception, several comparisons should be performed in randomized controlled trials (RCTs). To determine for male subfertility whether intrauterine insemination (IUI) improves the probability of conception compared with timed intercourse and whether the addition of controlled ovarian hyperstimulation influences the results. 1. The specialist database of the Cochrane Menstrual Disorders and Subfertility Group. 2. Medline search. 3. Embase search. 4. DDFU search. 5. BIOSIS search. 6. SCIsearch. 7. Manual searching of references mentioned in the obtained studies. 8. Personal communication and write letters to experts (14) in the field. 9. Abstracts of The American Society for Reproductive Medicine and European Society for Human Reproduction and Embryology Meetings. When important information is lacking from the original publications the authors will be contacted. Randomized controlled trials only. Independently by the first 2 authors: 1. Trial design characteristics. 2. Baseline characteristics of participants. 3. Types of intervention. 4. Outcomes where pregnancy is the outcome of main interest. Number of multiple pregnancies and number of cycles with ovarian hyperstimulation syndrome (OHSS) are secondary outcomes. Analysis of agreement between the two observers was determined for the following items: inclusion or exclusion of a trial, method of randomization, definition of male subfertility, design of the trial, number of pregnancies and completed cycles. Sensitivity analysis is performed. Seventeen trials fulfilled the selection criteria for this review and were included. Four trials are pending. Crude agreement concerning inclusion or exclusion of trials occurred for 41 of 43 (95%) trials reviewed (kappa 0.90). The included trials comprised 3,662 completed cycles. In natural cycles intrauterine insemination (IUI) significantly improved the probability of conception compared with timed intercourse (TI) (combined odds ratio with 95% confidence intervals: 2.43, 1.54 - 3.83). In cycles with controlled ovarian hyperstimulation (COH) IUI significantly improved the probability of conception also compared with TI (combined odds ratio with 95% confidence intervals: 2.14, 1.30 - 3.51). Despite clinical heterogeneity, these results are based on strong evidence. Intrauterine insemination in cycles with COH improved the probability of conception compared with IUI in natural cycles but significance was not reached (combined odds ratio with 95% confidence intervals: 1.79, 0.98 - 3.25). Comparing IUI in COH-cycles with TI in natural cycles the first treatment modality significantly improved the probability of conception (combined odds ratio with 95% confidence intervals: 6.23, 2.35 - 16.52). Intra-uterine insemination offers couples with male subfertility benefit over timed intercourse, both in natural cycles and in cycles with COH. In the case of a severe semen defect (with more than 1 million motile sperm after semen preparation and no triple sperm defect) IUI in natural cycles should be the treatment of first choice. The value of COH need to be further investigated in RCTs. Mild ovarian hyperstimulation with gonadotrophins is advised in cases with less sever