Male Factor Infertility Group Research Articles

P-366 Unraveling the whole transcriptome profiles of receptive phase endometrium in infertile women

Abstract Study question Are there differential transcriptomic profiles of the receptive phase endometria in infertile women with different infertility diagnoses? Summary answer Endometrium-related pathologies such as endometriosis and RIF seemed to share similar endometrial molecular profiles in mid-secretory phase,while samples from unexplained infertility were similar to controls. What is known already Successful embryo implantation is orchestrated by the combination of a viable blastocyst, a receptive endometrium and a perfectly synchronized molecular dialogue between them. Endometrium-associated pathologies such as endometriosis and recurrent implantation failure (RIF) are suggested to hamper endometrial receptivity, but the molecular mechanisms affected in these and other infertility diagnoses such as unexplained infertility need further investigation. Previous transcriptome studies of the human endometrium have analysed different infertility diagnoses separately, but whether and to what extent receptive-phase endometrial transcriptome profiles vary between distinct infertility diagnoses is underexplored. Study design, size, duration A prospective, cross-sectional study was performed at the Reproductive Unit at the University Hospital between March 2019 and April 2021. Forty-five well-characterized infertile women (age 34.7±3.8 years, BMI 24.5±kg/m2) were recruited before starting any infertility treatment. Four groups according to different infertility diagnoses were established: endometriosis (n = 12), RIF (n = 14), unexplained infertility (n = 10), and male factor infertility as control group (n = 9). Participants/materials, setting, methods Endometrial biopsies were collected using Pipelle curette during mid-secretory phase (LH + 7) of the natural cycle. Total RNA was extracted and sequenced using Illumina NovaSeq 6000 technology. Raw sequencing data was quality assessed, pre-processed and quantified, and differential expression and enrichment analyses were performed using R software. Main results and the role of chance Differential expression analysis revealed 743, 587 and 140 differentially expressed genes (DEGs) in endometriosis, RIF and unexplained infertility, respectively, when compared to control women of the male factor infertility group. Among these, 31 genes exhibited consistent differential expression between all infertility groups. Regarding functional enrichment analyses, the detected DEGs were mainly related to immune response and inflammatory processes, supporting the involvement of these pathways in the impairment of endometrial receptivity. Interestingly, the comparison between different study groups showed similar transcriptome profiles in endometrium-associated pathologies such as endometriosis and RIF, while women with unexplained infertility had similar molecular profiles with the control group of male factor infertility. These study results indicate common molecular pathways in endometrial receptivity between infertile women with endometriosis and RIF, and between unexplained infertility and control male factor infertility patients. Limitations, reasons for caution Further research with bigger sample size is required to confirm these findings. Wider implications of the findings We identified transcriptome profiles associated with infertility diagnoses. Further, women with unexplained infertility tended to have similar molecular profiles with control women, meaning that other factors than endometrial receptivity issues could lead to their infertility. Our study helps to understand the molecular mechanisms underlying female infertility in different infertility diagnoses. Trial registration number not applicable

The endometrial microbiota of women with or without a live birth within 12 months after a first failed IVF/ICSI cycle

The endometrial microbiota composition may be associated with implantation success. However, a ‘core’ composition has not yet been defined. This exploratory study analysed the endometrial microbiota by 16S rRNA sequencing (V1–V2 region) of 141 infertile women whose first IVF/ICSI cycle failed and compared the microbiota profiles of women with and without a live birth within 12 months of follow-up, and by infertility cause and type. Lactobacillus was the most abundant genus in the majority of samples. Women with a live birth compared to those without had significantly higher Lactobacillus crispatus relative abundance (RA) (p = 0.029), and a smaller proportion of them had ≤ 10% L. crispatus RA (42.1% and 70.4%, respectively; p = 0.015). A smaller proportion of women in the male factor infertility group had ≤ 10% L. crispatus RA compared to women in the unexplained and other infertility causes groups combined (p = 0.030). Women with primary infertility compared to secondary infertility had significantly higher L. crispatus RA (p = 0.004); lower proportions of them had ≤ 10% L. crispatus RA (p = 0.009) and > 10% Gardnerella vaginalis RA (p = 0.019). In conclusion, IVF/ICSI success may be associated with L. crispatus RA and secondary infertility with endometrial dysbiosis, more often than primary infertility. These hypotheses should be tested in rigorous well-powered longitudinal studies.

The effect of male and female factor infertility on women's anxiety, depression, self-esteem, quality of life and sexual function parameters: a prospective, cross-sectional study from Turkey.

Despite the development of diagnosis and treatment methods, the psychological effects of infertility on women were not adequately addressed. This study investigated the effect of male and female factor infertility on women's anxiety, depression, self-esteem, quality of life, and sexual function parameters. In this prospective, cross-sectional study, 480 women [n = 234, with male factor infertility (MFI) (MFI group) and n = 246, with female factor infertility (FFI) (FFI group)], who could not conceive despite unprotected intercourse for 1year, and 242 fertile healthy women (control group) who had children within the last 1year were included. Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), Rosenberg Self Esteem Scale (RSES), Fertility Quality of Life (FertiQol) and Female Sexual Function Index (FSFI) questionnaires were used for patients' evaluation. RSES, BAI and BDI-II scores were significantly higher and FSFI score was significantly lower in the FFI group compared to other groups. RSES, BAI and BDI-II scores were also significantly higher and FSFI score was significantly lower in the MFI group compared to the control group. FertiQol total score was significantly lower in the FFI group compared to the MFI group. RSES score was positively correlated with BDI-II and BAI scores; however, it was negatively correlated with FertiQol and FSFI scores. The negative psychological effects of infertility are ignored by many centres, especially in the treatment process of infertility. Regardless of the infertility factor (male or female), we believe that psychological support should be given to all women to improve their life quality.

Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.

We sought to determine whether pregnancies conceived in those with male factor infertility have unique placental pathology profiles compared to those undergoing infertility treatments for other indications. This was a retrospective cohort study of placental pathology from 464 live births conceived from autologous fresh IVF cycles at an academic fertility center from 2004 to 2017. Placental pathology was compared between live births arising from patients with male factor infertility alone and those with another infertility diagnosis. Placental outcomes were compared with parametric or non-parametric tests; logistic regression was performed to account for potential confounders. Compared to cycles performed for a non-male factor diagnosis, male factor infertility cycles had a higher mean paternal age (38.2years vs. 36.5years, p < 0.001), a higher female mean BMI (24.3 vs. 23.3kg/m2, p = 0.01), and a lower day 3 follicle stimulating hormone (FSH) level (6.8 vs. 7.3IU/mL, p = 0.02). The mean numbers of embryos transferred, and day of transfer were similar between groups, and more cycles used ICSI in the male factor infertility group (90.6% vs. 22.5%, p < 0.001). Placental pathology in our adjusted model was similar between the male factor and non-male factor groups. In our unadjusted subgroup analysis, cycles for male factor using ICSI appeared to lead to more small placentas by weight compared to cycles performed with conventional insemination (45.8% < 10th percentile vs. 18.8%, p = 0.04). Male factor infertility is not associated with significantly different placental pathology compared to other infertility diagnoses.

Serum Kisspeptin levels in unexplained infertility, polycystic ovary syndrome, and male factor infertility

Kisspeptin (KP), a hypothalamic peptide, is known as an important marker for neuroendocrine regulation during the human reproduction process. The unexplained infertility (UI) group comprised 30 patients, polycystic ovary syndrome (PCOS) group comprised 29 patients and the male factor infertility (MFI) group comprised 27 patients. An observational cohort study was conducted. The basic characteristics of the study population, BMI, and serum FSH, LH, E2, AMH, KP, TSH, and PRL levels and antral follicle count (AFC) on the 3rd menstruation day were evaluated. The mean KP level was 281.98 ± 73.9 ng/ml in the UI group, 525.49 ± 164.17 ng/ml in the PCOS group, and 354.313 ± 111.38 ng/ml in the MFI group (p < .001). KP levels were significantly higher in the PCOS group than in the UI and MFI groups (p < .001 for both). AUC was 83% (95% CI: 73%–93%), with 375.15 (pg/ml) as the cutoff value in the PCOS group with 83% sensitivity and 79% specificity. UI may be treated by KP injection therapies and higher levels of KP may be a reliable marker for AFC and diagnosis of PCOS. Clinical Trials registration number: NCT03018314

Spermatozoa Expression of piR-31704, piR-39888, and piR-40349 and Their Correlation to Sperm Concentration and Fertilization Rate After ICSI.

To investigate the relationship between spermatozoa PIWI-interacting RNAs (piRNAs) levels and semen parameters and to evaluate the role of expression of piRNAs on fertilization and embryo development after intracytoplasmic sperm injection (ICSI) treatment. One hundred and eighty-six patients with idiopathic male infertility who had undergone first ICSI cycles were enrolled in our study. The levels of piRNAs in spermatozoa were measured by real-time polymerase chain reaction. Semen parameters, including sperm concentration, motility, and morphology, were evaluated. The rates of fertilization, early cleavage, and day 3 good-quality embryo were calculated to assess embryo development potential. Spermatozoa levels of piR-31704 and piR-39888 were decreased in male factor infertility group as compared with control group (for piR-31704, P = .027 and for piR-39888, P = .041, respectively). And these 2 piRNAs were expressed at higher levels in patients with normal sperm concentration compared with subnormal sperm concentration group (for piR-31704, P = .042; for piR-39888, P = .047, respectively), while there were no correlation between the 3 piRNAs expression levels in spermatozoa and the rates of sperm progressive motility and normal sperm morphology. There were significant increases in the levels of all 3 piRNAs in spermatozoa from the group with higher 2PN rates (for piR-31704, P = .002; for piR-39888, P < .001; for piR-40349, P < .001; respectively), but there was no correlation between spermatozoa levels of these 3 piRNAs and the rates of embryo early cleavage, day 3 good-quality embryos and pregnancy. Spermatozoa piRNA levels correlate with sperm concentration and fertilization rate after ICSI. Paternal piRNAs may play a role in fertilization process.

Is early embryo cleavage a factor to increase success in all types of ICSI indications?

The authors aimed to compare early embryo cleavage with pregnancy rates in intracytoplasmic sperm injection/embryo transfer (ICSI/ET) cycles due to male infertility or tubal factor infertility (TFI). 412 ICSI/embryo transfer cycles undergoing treatment for over two years were prospectively analyzed; 337 of the cycles were due to male infertility, whereas 75 suffered from tubal factors. Non-early cleaved (NEC) embryos were used for ET in 271 male factor and 67 tubal factor cycles, whereas early cleavage embryos were used for embryo transfer in 66 male factor and eight tubal factor cycles. In 66 out of 337 cycles (19.58 %) in male factor group and in eight out of 75 tubal factor cycles (10.66%), early cleavage (EC) embryos were obtained (p = 0.069). The clinical pregnancy rate was significantly elevated in EC subgroup (34.8%) compared to NEC subgroup (20.6%) (p = 0.015) in the male factor infertility group. The clinical pregnancy rate was non-significantly elevated in EC subgroup (37.5%) compared to NEC subgroup (23.8%) (p = 0.410) in the TFI group. The authors found that the implantation and pregnancy success of EC embryos vary with the therapeutic indication. The success rate would be low even with usage of EC embryos in untreated cycles of TFI.

Decline in ovarian reserve may be an undiagnosed reason for unexplained infertility: a cohort study.

IntroductionUnexplained infertility refers to the absence of a definable cause for a couple’s failure to achieve pregnancy. Reproductive aging plays a role in pathogenesis of unexplained infertility. We investigated the results of ovarian reserve tests in unexplained infertility.Material and methodsThe patients were divided into two groups: unexplained infertility (n = 148) and male factor infertility (n = 112). Follicle-stimulating hormone, estradiol, inhibin b levels and anti-Müllerian hormone levels were evaluated. Antral follicle count and ovarian volume measurements were performed.ResultsThe demographic variables were comparable. Follicle-stimulating hormone levels were higher in the unexplained infertility group than the male factor infertility group, although this difference did not reach statistical significance (p = 0.071). Estradiol levels, inhibin b concentrations and ovarian volume showed no difference between groups. However, antral follicle count was significantly lower in the unexplained infertility group than the male factor infertility group (p = 0.023). The median anti-Müllerian hormone concentrations were significantly lower in the unexplained infertility group 1.42 (0.4–6.2) than in the male factor infertility group (2.04 (0.64–8.2); p = 0.001).ConclusionsAlthough anti-Müllerian hormone values and antral follicle count were higher than the low thresholds, a statistically significant decline of ovarian reserve in the unexplained infertility group was found in the present study. This might be an undiagnosed reason for unexplained infertility.

The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques

To investigate the association between follicular fluid homocysteine levels and embryo quality and pregnancy rates in patients undergoing assisted reproduction. Fifty infertile women who were admitted to our clinic were enrolled in the study. Ovulation induction was performed by using GnRH agonist and gonadotropins. For each patient, homocysteine level in the follicular fluid was measured by using nephelometric method after the oocyte pick-up. The association between the homocysteine concentration in the follicular fluid and the oocyte-embryo quality, pregnancy rates and hormone levels were investigated. Mean ± SD Hcy was 9.6 ± 2.02 μmol/L and 14.9 ± 2.93 μmol/L in pregnant and non-pregnant women, respectively (p < 0.0001). There were no statistically significant differences between pregnant and non-pregnant women in mean age, duration of infertility, body mass index, the oocyte-embryo quality parameters, and hormone levels. Homocystein did not have any correlation with M2, late M2, and total number of oocytes, number of fertilized oocytes and transferred embryos, and embryo quality grade. Area under curve (AUC) of hcy for prediction of pregnancy failure was 0.922 (p = 0.0001, 95% Confidence interval 0.85-0.99). A threshold of 11.9 μmol/L of hcy had a sensitivity of 82%, specificity of 100%, positive predictive value of 100% and negative predictive value of 91.6% for prediction of pregnancy failure. The subgroup analysis in male factor infertility group (n = 28), showed that mean homocystein was 9.9 ± 2.44 μmol/L and 14.1 ± 2.72 μmol/L in pregnant and non-pregnant women, respectively (p = 0.002). Low follicular fluid homocysteine level is associated with a better chance of clinical pregnancy.

Comparison of hysterosalpingography and hysteroscopy in the evaluation of the uterine cavity in patients undergoing assisted reproductive techniques

To investigate the diagnostic value of hysterosalpingography (HSG) for intracavitary and structural uterine pathologies in comparison with hysteroscopy (HS) in patients undergoing intracytoplasmic sperm injection-embryo transfer and also to specify the patients who should be subjected to HS in the early stages of an infertility work-up. Retrospective analysis. IVF unit of a university hospital. Three hundred fifty-nine consecutive women who underwent both HSG and HS for infertility investigation. HS and HSG. HS findings. HSG shows a sensitivity of 21.56%, specificity of 83.76%, positive predictive value of 55.26%, and negative predictive value of 70.75%. Its false-negative rate is 78.43%, and its false-positive rate is 16.23%. Overall agreement between the two procedures is 68.9%. The risk of abnormal HS increases with advancing patient age and duration of infertility. Risk increments associated with patient age over 35 years and increasing number of previous assisted reproductive techniques (ART) persist even in the presence of a normal HSG. As expected, we encounter significantly less abnormal HS in the male factor infertility group. HS should be performed especially in patients older than 35 years of age and/or with a history of two or more previous ART trials even in the presence of a normal HSG. HSG shows unconvincing diagnostic value for intracavitary and structural uterine pathologies in infertility evaluation.

Results of first in vitro fertilization cycle in women with colorectal endometriosis compared with those with tubal or male factor infertility

This retrospective study of women undergoing IVF (29 with colorectal endometriosis, 157 with tubal factor infertility, and 340 with male factor infertility) found similar fertility outcomes between the groups.

Poor sperm quality negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles

OBJECTIVE: Oocyte donation offers a powerful tool in the study of sperm quality, as oocyte and endometrial characteristics can be controlled and are comparable among the recipients. Since the introduction of intracytoplasmic sperm injection (ICSI), little attention is given to specific parameters of sperm function and their impact on IVF outcome. Our aim is to determine whether semen parameters influences embryo development and reproductive potential, and if they could be regarded as a prognostic factor in donor assisted reproductive technology cycles. DESIGN: Retrospective cohort analysis. MATERIALS AND METHODS: Three hundred and thirty two fresh ICSI cycles using donor oocytes were analyzed. ICSI was performed routinely to avoid inmature oocytes being given to the recipients. Only cycles in which >3 embryos were yielded and at least two Day3 good quality embryos were available for ET were included. Male partners were classified as normal (N), low-moderate (LM) or severe (S) male factor infertility according to the following sperm parameters: 1) Percent normal morphology by strict Kruger criteria: (S) <4%, (LM) 4-14%, (N)>14%, 2) Sperm concentration: (S) <10million/ml, (LM) 10- 20 million/ml, and (N) > 20million/ml, 3) Motility (L) <30%, (LM) 30-50%, (N) >50%, and 4) Post-preparation total motile count: (S) < 5 million, (LM) 5-10 million, and (N)>10 million sperm. Male factor infertility was correlated to a variety of outcome measures: embryo quality (day-3 cell cleavage, and fragmentation), fertilization, clinical pregnancy rate (CPR) and pregnancy loss. Statistical analysis was performed with chi2 for categorical data and t test for continuous parametric data. RESULTS: The number of fertilized oocytes and the number of day 3 embryos >7 cells was similar among the normal and low-moderate factor infertility group. However, the number of good quality embryos available for ET were significantly lower in the severe male factor infertility group (P<0.005). Implantation and clinical pregnancy rates were significantly decreased in this group when compared to male partners with normal or low-moderate semen parameters: Normal CPR 52,05% (76/146), Low-Moderate CPR 40,91%, Severe CPR 29,63% (16/54) (p<0.05). CONCLUSIONS: Poor sperm quality was negatively associated with reproductive outcomes in oocyte donation cycles suggesting a paternal influence on embryo development in which ICSI may not be able to select the sperm of highest quality for oocyte injection.

Survivin gene expression in granulosa cells from infertile patients undergoing in vitro fertilization–embryo transfer

To evaluate survivin gene expression in granulosa cells from infertile patients and examine the relationship between survivin gene expression and infertile clinical background. Prospective study. IVF-ET program at Osaka Medical College. Twenty-eight patients underwent ovulation induction for IVF-ET performed because of tubal infertility, male factor infertility, or endometriosis. Granulosa cells obtained at oocyte retrieval were examined for survivin gene expression by quantitative reverse transcription-polymerase chain reaction. Hormone environment, number of oocytes, fertilization rate, high-quality embryo rate, pregnancy rate, and expression of survivin genes. Survivin gene expression was detected in all granulosa cells. The gene expression levels of survivin in patients with endometriosis were significantly lower than those in patients with male factor infertility. The gene expression levels of survivin in total pregnant patients were higher than those in total nonpregnant patients and than those in the male factor infertility group, and there was no correlation between gene expression level and serum E(2) level. Survivin may be used as an indicator of the success of IVF-ET, and the existence of endometriosis may elevate the apoptosis of granulosa cells.

Development of a sensitive enzyme immunoassay for anti‐Müllerian hormone and the evaluation of potential clinical applications in males and females

Recent studies have found anti-Müllerian hormone (AMH) to be a potentially important marker for the assessment of ovarian reserve and prediction of the success of in vitro fertilization (IVF) treatment. The objectives of this study were to develop a sensitive and specific assay for AMH and to evaluate the potential application of the assay. This assay will be then available to our collaborators in the UK and overseas. Samples obtained as part of another prospective cross-sectional study from infertility patients and another prospective longitudinal study from pregnant women were used in this study to measure AMH using a new double-antibody enzyme-linked immunosorbent assay (ELISA). AMH levels were evaluated in (i) serum and seminal fluid from males (normal and male factor infertility males), (ii) serum and follicular fluid from females (normal and female with unexplained infertility) and (iii) serum, amniotic fluid (AF) and coelomic fluid (CF) from pregnant women. AMH levels in the samples were measured by a newly developed ELISA. The assay had a detection limit of<0.078 ng/ml. High recoveries of spiked recombinant protein were observed from male and female sera and also from follicular, seminal, coelomic and amniotic fluids. The intra- and interassay coefficients of variation (CVs) were 3.6% and 4.0%, respectively. Serially diluted human samples gave dose-response curves parallel to the standard curve. Immunoreactivity was stable to sample storage at room temperature for several days and to multiple cycles of freezing and thawing. In seminal fluid, the AMH concentrations in a group of men with male factor infertility were insignificantly different from those in fertile men. By contrast, serum AMH concentrations were lower in the male factor infertility group than the normal group of patients. Women with unexplained infertility had similar concentrations of AMH in serum and follicular fluid compared to controls. Pregnant women had higher concentrations of AMH in the circulation in early pregnancy compared with nonpregnant women, suggesting a foeto-placental contribution and a possible biological role for this molecule in early pregnancy. We have developed a sensitive and specific assay for AMH. Serum AMH in men with male factor infertility is lower than in normal men. Levels of AMH in pregnancy are higher than normal menstrual cycle levels suggesting a foeto-placental contribution.

Life-table analysis of artificial insemination pregnancy rates for couples with male factor and idiopathic infertility.

Background: In the summer of 2002, standard guidelines for the application of assisted reproductive technology were reported by a research group of the Ministry of Health, Labor and Welfare. The present study aimed to examine the relationship between the number of cycles of artificial insemination and the cumulative pregnancy rates according to the cause of infertility. Methods: Patients who experienced their first cycle of artificial insemination during the period of January 1999-December 2002 were included in the study and were divided into a male factor infertility group and an idiopathic infertility group. Cumulative pregnancy rates resulting from artificial insemination with the husband's semen were calculated by the life-table approach. Results: During the study period, 139 couples entered the assisted reproduction program and underwent 581 cycles. Significant differences were observed in cumulative pregnancy rates between the two groups. Conclusion: It is recommended that couples with male factor infertility and who fail to conceive within six or seven cycles of intrauterine insemination, consider a modification of treatment strategy such as in vitro fertilization, because cumulative pregnancy rates of this group were reached at a plateau within six or seven cycles. In contrast, patients with idiopathic infertility, the cumulative pregnancy rates appeared to increase constantly with each subsequent cycle. It is important to consider modifications of treatment strategy in the light of the cause of infertility. (Reprod Med Biol 2004; 3: 27-31).

Isolated teratozoospermia and intrauterine insemination

Objective This study tests the hypothesis that IUI treatment in cases with isolated teratozoospermia (<10% normal forms using strict criteria, normal motility and normal count), results in a lower cumulative live birth rate compared to cases with normozoospermia. Design A retrospective cohort study. Setting An academic fertility center. Patient(s) Eight hundred seventy-two IUI cycles in 440 couples were analyzed. Intervention(s) Couples (n = 440) were classified in three groups: normozoospermia (n = 213), isolated teratozoospermia (n = 104), and male factor infertility (n = 123). Main outcome measure(s) Live birth rate per cycle and cumulative live birth rate (CLBR). Result(s) The three groups were similar with regard to female age, female infertility factors, and ovarian response after hormonal stimulation. The overall CLBR after four cycles was 41.5%, and was significantly increased in the normozoospermic group (52.8%) when compared to the isolated teratozoospermia group (33.4%) and the male factor infertility group (31.4%). Conclusion(s) This study documents for the first time that the CLBR after four IUI cycles is significantly and similarly reduced in couples with isolated teratozoospermia as in couples with other sperm defects, when compared to couples with normozoospermia. As with couples with male factor infertility, couples with isolated teratozoospermia should be counseled about other treatment options such as IVF, as the CLBR after three IVF cycles is 70%–80% in our program.

Clomiphene citrate ovulation induction in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone versus human chorionic gonadotropin timing

To evaluate the clinical pregnancy rates (PRs) in anovulatory, male factor, and unexplained infertility using clomiphene citrate (CC) with an IUI and to evaluate the difference in PRs between urinary LH testing and hCG administration for timing of the IUI. Retrospective clinical study. Academic, tertiary care fertility center. One hundred thirty-eight couples (432 cycles) undergoing IUI with CC ovulation induction as a treatment for unexplained, anovulatory, or male factor infertility were selected. All women with unexplained or male factor infertility received CC at a dose of 50 mg/d, and those with anovulation received CC at a dose ranging from 50 to 200 mg/d. All women in the study received a single IUI either the morning after a urinary LH surge or 36 to 38 hours after an evening hCG injection. Clinical PR. There were no differences in the clinical PRs between LH testing or hCG administration in any of the three groups. Clinical PRs were extremely low in the male factor infertility group regardless of the timing used. These data suggest that the success of IUI with CC is not dependent on the method used to establish the timing for the IUI. In couples undergoing IUI with CC, the use of urinary LH testing may result in lower costs by reducing patient visits and the midcycle ultrasound.

Evaluation of clomiphene citrate and human chorionic gonadotropin treatment: a prospective, randomized, crossover study during intrauterine insemination cycles

To test the hypothesis that in couples undergoing IUI, actively managed cycles using clomiphene citrate (CC) stimulation, ultrasound monitoring, and hCG timing will result in increased pregnancy rate (PR) per cycle compared with unstimulated urinary LH-timed cycles. Fifty-six couples with unexplained infertility (n = 26) or male factor infertility (n = 30) participated in the study. Tertiary academic medical center. Prospective, randomized, crossover. Couples were randomized initially to one of the two study groups (treatment A: LH-timed IUI; treatment B: CC-stimulated, hCG-timed IUI). If no pregnancy occurred, each couple alternated between the two regimens during subsequent cycles, up to a total of four cycles. Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group, one pregnancy occurred during the 26 cycles of each treatment group (PR per cycle of 3.9% for both treatment groups). In contrast, among the unexplained infertility group, there was a marked difference in the effect of treatments. During treatment A only one pregnancy occurred in 20 cycles (PR of 5% per cycle) whereas during treatment B, six pregnancies occurred in 23 cycles (PR of 26.1% per cycle). If IUI is chosen as the treatment modality in unexplained infertility, the addition of active ovulation management that includes CC stimulation, ultrasound monitoring of folliculogenesis, and hCG timing of ovulation increases the PR per cycle. In couples with male infertility, PR per cycle is low and is apparently not affected by the addition of active ovulation management.

Increased Pregnancy Rate with Oil-Soluble Hysterosalpingography Dye

The diagnostic value of hysterosalpingography remains unquestioned. Previous studies have suggested that patients who underwent hysterosalpingography with an oil-soluble contrast medium (OSCM) rather than a water-soluble contrast medium (WSCM) had higher subsequent fertility rates. This study evaluated subsequent fertility rates in 339 patients who underwent hysterosalpingography in which OSCM or WSCM was used. All forms of infertility were included and over-all, pregnancy occurred in the WSCM group in 21 of 162 patients (13%), in the OSCM group in 51 of 177 patients (29%); these rates were significantly different (P < 0.001), with the unexplained infertility group and the male factor infertility group showing the most significant difference. Adverse effects of OSCM hysterosalpingography were not corroborated. For this reason it is suggested that initially the patient undergo hysterosalpingography with WSCM. Once patency has been established, 3 ml of OSCM should be injected as a therapeutic modality to increase subsequent fertility.