New insights regarding origin of monosomy occurrence in early developing embryos as demonstrated in preimplantation genetic testing.

INTRODUCTION: Analyses of miscarriage products indicate that the majority of aneuploidies in early developing embryos derive from errors occurring during maternal meiosis and the paternal contribution is less than 10%. Our aim was to assess the aneuploidy (mainly monosmies) frequencies at the earliest stages of embryo development, 3 days following fertilization during In vitro fertilization (IVF) treatments and to elucidate their parental origin. Later, we compared monosomies rates of day 3 to those of day 5 as demonstrated from Preimplantation Genetic Testing for Structural chromosomal Rearrangement (PGT-SR) results. METHODS: For a retrospective study, we collected data of 210 Preimplantation Genetic Testing for Monogenic Disorder (PGT-M) cycles performed between years 2008 and 2019.This study includes 2083 embryos, of 113 couples. It also included 432 embryos from 90 PGT-SR cycles of other 45 patients, carriers of balanced translocations. Defining the parental origin of aneuploidy in cleavage stage embryos was based on haplotypes analysis of at least six informative markers flanking the analyzed gene. For comprehensive chromosomal screening (CCS), chromosomal microarray (CMA) and next generation sequencing (NGS) was used. RESULTS: We inspected haplotype data of 40 genomic regions, flanking analyzed genes located on 9 different chromosomes.151 (7.2%) embryos presented numerical alterations in the tested chromosomes. We found similar paternal and maternal contribution to monosomy at cleavage stage. We demonstrated paternal origin in 51.5% of the monosomy, and maternal origin in 48.5% of the monosomies cases. CONCLUSION: In our study, we found equal parental contribution to monosomies in cleavage-stage embryos. Comparison to CCS analyses of PGT-SR patients revealed a lower rate of monosomy per chromosome in embryos at day 5 of development. This is in contrast to the maternal dominancy described in studies of early miscarriage. Mitotic errors and paternal involvement in chemical pregnancies and IVF failure should be re-evaluated. Our results show monosomies are relatively common and may play a role in early development of ART embryos.

Functional ovarian reserve in transgender men receiving testosterone therapy: evidence for preserved anti-Müllerian hormone and antral follicle count under prolonged treatment.

STUDY QUESTION: Is the functional ovarian reserve in transgender men affected by testosterone therapy? SUMMARY ANSWER: Serum anti-Müllerian Hormone (AMH) levels slightly decrease during testosterone treatment but remain within the normal range, suggesting preserved follicular ovarian reserve. WHAT IS KNOWN ALREADY: Few small studies have investigated the impact of gender-affirming treatment on reproduction in transgender men. Conflicting results were reached concerning ovarian morphology and AMH levels in this context. STUDY DESIGN, SIZE, DURATION: The study consisted of two arms. The first arm was a prospective pilot study, which enrolled 56 transgender men (median age 22.5 [interquartile range (IQR)-19-27.7] years), 27 of whom had polycystic ovary syndrome (PCOS), prior to the initiation of gender-affirming testosterone therapy. A structured assessment was conducted prior to, and at 3 and 12 months after treatment initiation. The second arm was a cross-sectional study that comprised 47 transgender men (median age 24 [IQR-20-31] years) who received testosterone for a median duration of 35 [IQR 13-62] months. The main outcome measures were serum AMH and antral follicle count (AFC) as indices of ovarian follicular reserve. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at a tertiary center for transgender health. Gender-affirming therapy was administered according to standard practice. AFC was determined by pelvic (abdominal or transvaginal) ultrasound and blood collection for measurements of AMH, testosterone, estradiol, LH and FSH was performed at the designated time-points. MAIN RESULTS AND THE ROLE OF CHANCE: Prospective arm for the entire group we observed a decrease of 0.71 ng/ml in AMH levels between baseline and 12 months (P = 0.01). When expressed in age-specific percentiles, AMH went from the 47.37th to the 40.25th percentile at 12 months (P < 0.001). In a sub-group analysis, a decline of 9.52 points in age-specific percentile was seen in subjects with PCOS (P < 0.001), while no changes were detected in the non-PCOS group. Testosterone treatment did not affect AFC over time in the entire cohort. In the sub-group analysis, a mean decrease of 5.0 follicles was detected between baseline and the 12 months assessment (P = 0.047) only in subjects with PCOS. In the cross-sectional study, AMH inversely correlated with age but not with treatment duration. Notably AMH did not deviate from the 50th age-specific percentile. Finally, four men fathered biological children after being under testosterone treatment for up to 12 years. LIMITATIONS, REASONS FOR CAUTION: The limited sample size of the pilot study should be kept in mind. An additional limitation is the lack of a control group in the prospective study, as each participant served as his own control. Also, roughly 40% of the ultrasound examinations were performed transabdominally, potentially affecting the accuracy of the AFC measurements.As study participants were quite young, our reassuring data may not apply to older transgender men, either because of an age-related decline in ovarian reserve or to possible long-term effects of testosterone therapy. Furthermore, the chances for fertility preservation may be more limited in subjects with PCOS. WIDER IMPLICATIONS OF THE FINDINGS: This is an additional contribution to the emerging evidence that prolonged testosterone treatment may not be a major obstacle to later fertility potential in transgender men desirous of having children. Larger confirmatory studies, and particularly more with reproductive outcome data, are needed for evidence-based fertility counseling prior to treatment initiation in these subjects. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Novel agents for the treatment of lymphomas during pregnancy: A comprehensive literature review.

Lymphoproliferative diseases occurring during pregnancy present unique diagnostic and therapeutic challenges aiming to achieve maternal cure without impairing fetal health, growth, and survival. These goals are further complicated by the fast-paced emergence of novel therapies and their introduction as standard of care, even in newly diagnosed patients. Due to the rarity of hematological malignancies in pregnancy and the exclusion of pregnancy in almost all clinical trials, available data on the fetal effects of novel drugs are limited to animal models and case reports. The current review addresses the entire multidisciplinary team involved in treating pregnant patients with lymphoproliferative diseases. We describe novel agents according to their mechanism of action, and summarize our knowledge of their effects during the gestational period, particularly those associated with fetotoxicity. Therapeutic dilemmas associated with the employment of these new agents are also discussed.

Automated Measurements of Key Morphological Features of Human Embryos for IVF.

A major challenge in clinical In-Vitro Fertilization (IVF) is selecting the highest quality embryo to transfer to the patient in the hopes of achieving a pregnancy. Time-lapse microscopy provides clinicians with a wealth of information for selecting embryos. However, the resulting movies of embryos are currently analyzed manually, which is time consuming and subjective. Here, we automate feature extraction of time-lapse microscopy of human embryos with a machine-learning pipeline of five convolutional neural networks (CNNs). Our pipeline consists of (1) semantic segmentation of the regions of the embryo, (2) regression predictions of fragment severity, (3) classification of the developmental stage, and object instance segmentation of (4) cells and (5) pronuclei. Our approach greatly speeds up the measurement of quantitative, biologically relevant features that may aid in embryo selection.

Optimal timing for blastomere biopsy of 8-cell embryos for preimplantation genetic diagnosis.

STUDY QUESTION: What is the optimal timing for blastomere biopsy during the 8-cell stage, at which embryos will have the best implantation potential? SUMMARY ANSWER: Fast-cleaving embryos that are biopsied during the last quarter (Q4) of the 8-cell stage and are less affected by the biopsy procedure, and their implantation potential is better than that of embryos biopsied earlier during the 8-cell stage (Q1-Q3). WHAT IS KNOWN ALREADY: Blastomer biopsy from cleavage-stage embryos is usually performed on the morning of Day 3 when the embryos are at the 6- to 8-cell stage and is still the preferred biopsy method for preimplantation genetic diagnosis (PGD) for monogentic disorders or chromosomal translocations. Human embryos usually remain at the 8-cell stage for a relatively long 'arrest phase' in which cells grow, duplicate their DNA and synthesize various proteins in preparation for the subsequent division. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study. The study group (195 embryos) included all 8-cell stage embryos that underwent blastomere biopsy for PGD for monogenetic disorders and chromosomal translocations in our unit between 2012-2014 and cultured in the EmbryoScope until transfer. The control group (115 embryos) included all embryos that underwent intracytoplasmic sperm injection without a biopsy during the same period. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 8-cell stage was divided into four quarters: the first 5 h post-t8 (Q1), 5-10 h post-t8 (Q2), 10-15 h post-t8 (Q3) and at 15-20 h post-t8 (Q4). Non-biopsied control embryos were divided into four equivalent quarters. Embryos were evaluated for timing of developmental events following biopsy including timing of first cleavge after biopsy, timing of comapction (tM) and start of blastulation (tSB). Timing of these events were compared between PGD and control embryos, as well as with 56 PGD implanted embryos with Known Implantation Data (PGD-KID-positive embryos). MAIN RESULTS AND THE ROLE OF CHANCE: Embryos that were biopsied during Q3 (10-15 h from entry into 8-cell stage) were delayed in all three subsequent developmental events, including first cleavage after biopsy, compaction and start of blastulation. In contrast, these events occurred exactly at the same time as in the control group, in embryos that were biopsied during Q1, Q2 or Q4 of the 8-cell stage. The results show also that embryos that were biopsied during Q1, Q2 or Q3 of the 8-cell stage demonstrated a significant delay from the biopsied implanted embryos already in t8 as well as in tM and tSB. However, embryos that were biopsied during Q4 demonstrated dynamics similar to those of the biopsied implanted embryos in t8 and tM, and a delay was noticed only in the last stage of tSB. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study that is limited to the timing of biopsy that is routinely performed in the IVF lab. A prospective study in which biopsy will be performed at a desired timing is needed in order to differ between the effect of biopsy itself and the cleavage rate of the embryo. WIDER IMPLICATIONS OF THE FINDINGS: Our findings showed that blastomere biopsy can be less harmful to further development if it is carried out during a critical period of embryonic growth, i.e during Q4 of the 8-cell stage. They also demonstrated the added value of time-lapse microscopy for determining the optimal timing for blastomere biopsy. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the routine budget of our IVF unit. TRIAL REGISTRATION NUMBER: N/A.

Mechanical properties and biocompatibility of the sputtered Ti doped hydroxyapatite.

The hydroxyapatite enriched with Ti were prepared as possible candidates for biomedical applications especially for implantable devices that are in direct contact to the bone. The hydroxyapatites with different Ti content were prepared by RF magnetron sputtering on Ti-6Al-4V alloy using pure hydroxyapatite and TiO2 targets. The content of Ti was modified by changing the RF power fed on TiO2 target. The XPS and FTIR analyses revealed the presence of hydroxyapatite structure. The hardness and elastic modulus of the hydroxyapatite were increased by Ti addition. After 5 days of culture, the cell viability of the Ti-6Al-4V was enhanced by depositing with undoped or doped hydroxyapatite. The Ti additions led to an increase in cell viability of hydroxyapatite, after 5 days of culture. The electron microscopy showed the presence of more cells on the surface of Ti-enriched hydroxyapatite than those observed on the surface of the uncoated alloys or undoped hydroxyapatite.

Enhancement of the mechanical properties of hydroxyapatite by SiC addition.

Improvements of mechanical and anticorrosive properties, as well as superior osseointegration of the hydroxyapatite coated titanium alloy were reported in the last years by the addition of different elements (Si or Ti) into hydroxyapatite structure. The aim of this work was to prepare and to investigate the hydroxyapatite (HAP) coatings enriched with SiC in order to enhance the mechanical properties of HAP films. The coatings were deposited on Ti6Al4V alloy substrates by co-sputtering of HAP and SiC targets, using a magnetron sputtering system. The films were characterized in terms of elemental and phase composition, chemical binding, morphology and mechanical properties by EDS, XRD, FTIR, SEM, AFM, and nanoindentation. Overall, improved mechanical properties were found by adding SiC to the basic HAP structure.

Interval double transfer improves treatment success in patients with repeated IVF/ET failures.

PURPOSE: To examine whether double transfer of embryos on day 2-3 and on day 5 after ovum pick-up (OPU) improves IVF/ET success rates in patients with multiple consecutive IVF failures METHODS: Consecutive IVF failures patients (7.6 +/- 0.5) undergoing IVF/ET cycles were treated with interval double transfer on day 2-3 and on day 5 after OPU. Matched patients, that had embryos transferred only once on day 2 or 3 served as controls. RESULTS: Baseline and cycle characteristics were similar in the study group and controls. The total pregnancy rate was 44.6% in the study group and 24.2% in the controls (p = 0.001), and the clinical pregnancy rates were 38.5% and 19.6%, respectively (p = 0.001). CONCLUSIONS: Patients with multiple consecutive IVF/ET failures, treated with the interval double transfer approach had significantly improved cycle success rates compared with regular day 2 or 3 embryo transfer protocol.

Pregnancy after laparoscopic adjustable gastric banding: perinatal outcome is favorable also for women with relatively high gestational weight gain.

BACKGROUND: The prevalence of morbid obesity is increasing steadily among women of reproductive age. In addition to the well-known comorbidities of the disease, it has been shown that the pregnancy outcome for obese women is worse than for women with a normal body mass index. This study aimed to evaluate the pregnancy and perinatal outcomes for women who underwent laparoscopic adjustable gastric banding (LAGB) because of morbid obesity. METHODS: This prospective, population-based study was conducted in a general surgery clinic of a tertiary hospital serving as a referral center for bariatric operations. All the patients underwent LAGB by the pars flaccida technique. A database containing information regarding age, pre- and postoperative weight and body mass index, weight gain, and LAGB-related or -unrelated complications during pregnancy was constructed for all women of childbearing age who underwent LAGB. A questionnaire was designed to provide perinatal data concerning both mother and neonate. RESULTS: The 74 women enrolled in this study had 81 single tone pregnancies. Their body mass index decreased significantly after LAGB, from 43.3 +/- 5.8 to 30.3 +/- 3 kg/m2 at conception (p < 0.0001). The average time to the first live birth after surgery was 27 +/- 3 months. Band slippage was diagnosed and treated laparoscopically in two patients (2.4%). Weight gain during pregnancy was 10.6 +/- 2.1 kg. The rates of pregnancy-induced hypertension and gestational diabetes were 7.4% and 16% of all pregnancies, respectively. In 17 cases (20%), cesarean section was performed. Delivery occurred after 39.1 weeks of gestation. The mean birth weight was 3.09 +/- 0.5 kg. Major congenital anomalies, postnatal hypoglycemia, symptomatic polycythemia or neonatal death were not recorded. CONCLUSIONS: The findings show that LAGB is safe for both mother and newborn during gestation and delivery.

Apoptosis in cryopreserved human ovarian tissue obtained from cancer patients: a tool for evaluating cryopreservation utility.

Fertility preservation is of major importance for women with cancer in whom ovarian function may be disturbed by the use of potentially sterilizing chemotherapeutic drugs and/or pelvic irradiation. Cryopreservation of ovarian cortical tissue is one of the potential options for preserving fertility among these women. Cryopreserved thawed human ovarian tissue can be autografted either orthotopically or heterotopically, but may also be transplanted first into an animal host with subsequent maturation and collection of oocytes. The objective of this study was to investigate the prevalence of ovarian follicular apoptosis in fresh and frozen/ thawed human ovarian tissue as a measure of follicular viability. The study group included 6 women with cancer who underwent ovarian tissue cryopreservation (OTCP). Ovarian tissue samples (n = 2) were obtained from each woman with one sample undergoing evaluation for apoptosis immediately following removal (control, group A) and the other evaluated for apoptosis following freezing/thawing (group B). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and 4'6' diamido-2-phenylindole hydrochloride (DAPI) staining methods were used to investigate follicular apoptosis. Morphological changes in the same samples were evaluated in hematoxylin and eosin (H&E)-stained sections. In each slide, only primordial and primary follicles were evaluated for abnormal morphology and apoptosis. Abnormal morphology was demonstrated in 23.8+/-8.7% of group A follicles compared to 48.3+/-11.2% of group B follicles (p < 0.05). Apoptosis was demonstrated in 25.4+/-8.4% of group A follicles compared to 60.9+/-6.0% of group B follicles (p < 0.05). We have shown that the ovarian follicles in group B demonstrated a higher incidence of apoptosis compared to those of group A. Therefore, the data suggest that follicular apoptosis might be a consequence of the freezing and thawing procedure. This may be used as a method for evaluating and comparing the outcome of different freezing/thawing protocols.

Interleukin-18 is high in the serum of IVF pregnancies with ovarian hyperstimulation syndrome.

PROBLEM: The presence of interleukin-18 (IL-18) in serum and pre-ovulatory follicular fluid (FF) and its possible correlation to in-vitro fertilization/embryo transfer (IVF/ET) outcome and ovarian hyperstimulation syndrome (OHSS) development. METHOD OF STUDY: A prospective study was carried out. Assays for serum and pooled pre-ovulatory FF levels of IL-18 were performed on 30 patients who underwent oocyte retrieval for IVF/ET. RESULTS: Mean serum and FF levels of IL-18 were 370.4 +/- 224 and 228.9 +/- 208 pg/mL, respectively (r = 0.77, P < 0.0001). Levels of FF IL-18 were comparable between the two ovaries (right = 221 +/- 166.8 pg/mL, left = 237 +/- 171.9 pg/mL; r = 0.7550, P = 0.49). A positive correlation was found between IL-18 FF levels and number of retrieved oocytes (r = 0.45; P = 0.019). In three patients (10%) who developed OHSS, the mean serum level of IL-18 at day of ovum pickup was significantly higher compared with patients without OHSS (620 +/- 196 pg/mL versus 345 +/- 251 pg/mL, respectively, P = 0.04). CONCLUSIONS: Both pre-ovulatory FF and serum levels of IL-18 correlate with the number of retrieved oocytes. The serum IL-18 level at day of ovum pickup may predict consequent development of OHSS. Further investigations are warranted to determine the role of IL-18 in the folliculogenesis and OHSS pathogenesis.

Spindle imaging: a new marker for optimal timing of ICSI?

BACKGROUND: The LC Polscope facilitates visualization of the meiotic spindle in human oocyte. This study aimed to investigate meiotic spindle assembly in correlation to time elapsed after HCG administration, and to determine whether spindle imaging may serve to indicate the likelihood of fertilization and embryo cleavage. METHODS: Metaphase II (MII) oocytes from 103 couples who were being treated for male infertility were imaged with the Polscope prior to sperm injection. Spindle imaging was correlated to time elapsed from HCG administration, fertilization rate and embryo cleavage. The main outcome measures were spindle visualization, fertilization and embryo cleavage on day 3. RESULTS: A total of 770 MII oocytes were imaged. A spindle was imaged in a significantly higher number of oocytes from >or=38 h after HCG administration compared with those in the <38 h group (78.1-81.5% versus 61.6%; P < 0.001). The fertilization rate in oocytes with a visible spindle was statistically higher compared with oocytes in which spindle could not be detected (70.4% versus 62.2%; P = 0.035). We found no relationship between spindle imaging and embryo cleavage on day 3. CONCLUSIONS: Spindle imaging, in addition to first polar body appearance, is an accurate indicator for oocyte maturity. We suggest that spindle imaging be performed prior to sperm injection.

The mechanism of hydrosalpinx in embryo implantation.

BACKGROUND: Hydrosalpinx adversely affects embryo implantation and contributes to poor implantation rates post embryo transfer. Embryo transport depends on concomitant intrauterine fluid motion induced by uterine wall motility, the result of spontaneous myometrial contractions towards the fundus. METHODS AND RESULTS: The uterine dynamics of five patients with hydrosalpinx were recorded and analysed by image-processing techniques: the frequency was higher while the amplitudes and passive widths were lower compared with healthy volunteers. The existing peristaltic activity should have induced intrauterine fluid flow; however, the recordings failed to show the expected transport of fluid bolus. This observation was supported by mathematical simulations based on the hypothesis that fluid accumulation in the Fallopian tube of a patient with hydrosalpinx increases tubal pressure and thereby induces a pressure gradient between the fundus and the cervix. This pressure gradient acts adversely to the cervix-to-fundus intrauterine peristalsis and generates reflux currents that may thrust embryos away from the implantation site. CONCLUSIONS: The reflux phenomenon could explain the reduced implantation rate associated with hydrosalpinx. Resolution of the issue of whether the removal of a Fallopian tube with hydrosalpinx should be undertaken for improving IVF pregnancy rates should be accompanied by prospective randomized clinical trials.

The interrelationship between coping strategies and sexual functioning in in vitro fertilization patients.

This study examined the correlation between various coping strategies and sexual functioning and the likelihood of conception from in vitro fertilization (IVF). Self-reported questionnaires were distributed randomly among the 102 women enrolled in an IVF program, 96 of whom were recruited. Of the studied parameters, positive reinterpretation, and growth, and active coping strategies were found to be positively associated with sexual functioning, while there was a significantly (p < .05) adverse influence of planning and self-restraint. Being sexually active during the IVF-treatment period was found to be positively associated (p < .05) with the likelihood of conception and with adaptive coping strategies.

Increasing synthetic serum substitute (SSS) concentrations in P1 glucose/phosphate-free medium improves implantation rate: a comparative study.

PURPOSE: To assess the comparative efficacy of IVF medium (MediCult, with 5.2 mM glucose) and a glucose/phosphate-free medium, P1 (Irvine Scientific), and to investigate the influence of increasing the serum supplementation (synthetic serum substitute; SSS; Irvine Scientific) to P1 on embryo development and implantation. METHODS: Patients were randomly assigned to IVF medium (Group 1, cycles n = 172) or P1 supplemented with 10% SSS (Group 2, cycles n = 229) according to the medium scheduled for use on the day of oocyte retrieval. Another 555 IVF consequent cycles (Group 3) were performed using increased SSS concentrations (20%) in P1 medium. RESULTS AND CONCLUSION: In this large series of IVF cycles, we herein demonstrate that significantly higher pregnancy and implantation rates were found when embryos were cultured in glucose/phosphate-free medium P1 supplemented with 20% SSS compared to supplementation with the lower SSS concentration and with IVF medium.

Does ICSI affect early serum beta-HCG in pregnancies achieved after IVF?

This study was conducted to compare early serum human chorionic gonadotrophin (HCG) concentrations in singleton pregnancies achieved after intracytoplasmic sperm injection (ICSI), with those achieved after conventional in-vitro fertilization (IVF). Early serum HCG, 14-16 days after embryo transfer, was analysed in 99 IVF pregnancies achieved after ICSI (group A), and compared to 105 conventional IVF pregnancies (group B). All women were treated at the IVF Unit, Lis Maternity Hospital. Records were studied retrospectively. The mean +/- SE serum HCG concentration on day 14 after embryo transfer in group A was 190.5 +/- 17.4 mIU/ml, compared to 195.7 +/- 14.03 mIU/ml in group B. HCG concentration 14 days after embryo transfer in both groups A and B was higher in women with mechanical factor than in couples with male factor infertility or unexplained infertility (246 +/- 31.4, 183.3 +/- 16.4, 177.98 +/- 14.3 mIU/ml respectively). On the 16th day after embryo transfer, the HCG concentration increased, and the difference between the groups was maintained. Only in the subgroup of unexplained infertility did we find a difference in concentrations of HCG between ICSI and conventional IVF: on the 16th day following embryo transfer in this group there was a significant difference in HCG concentrations (395. 8 +/- 21 and 545.6 +/- 45.7 respectively; P = 0.04). HCG concentrations did not differ overall in the conventional IVF pregnancies compared with those achieved by ICSI. However, a statistical difference in early serum HCG concentrations was found in relation to the aetiology of infertility.

Vertebral osteomyelitis: a rare complication of transvaginal ultrasound-guided oocyte retrieval.

OBJECTIVE: To present a case of vertebral osteomyelitis as a complication of transvaginal oocyte retrieval. DESIGN: Case report. SETTING: The IVF unit of a university-affiliated hospital. PATIENT(S): A 41-year-old woman who underwent IVF-ET treatment. INTERVENTION(S): Standard IVF-ET treatment cycles with the use of transvaginal ultrasound for oocyte retrieval and computed tomography-guided needle aspiration. MAIN OUTCOME MEASURE(S): Recovery of the patient, sequelae, and recurrence. RESULT(S): Vertebral osteomyelitis was diagnosed and treated with antibiotics. CONCLUSION(S): When severe low back pain occurs after ovum retrieval, vertebral osteomyelitis should be considered. Early diagnosis requires a high index of suspicion.

Intrauterine insemination before transfer of frozen-thawed embryos may improve the pregnancy rate for couples with unexplained infertility: preliminary results of a randomized prospective study.

OBJECTIVE: To evaluate whether a combination of IUI and frozen-thawed embryo transfer (FT-ET) with ovulation induction would improve the PR in couples with unexplained infertility. DESIGN: Prospective, randomized study. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): Sixty-two patients with unexplained infertility were assigned into two groups. The study group was composed of 32 women (38 cycles) who received ovulation induction followed by IUI and FT-ET. The control group was composed of 30 women (33 cycles) who received ovulation induction followed by FT-ET. INTERVENTION(S): Clomiphene citrate (CC) and hCG, IUI, and FT-ET. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) per cycle, PR per ET. RESULT(S): In the study group, the PR per cycle and per ET were 36.8% (14 of 38) and 40.6% (13 of 32), respectively. In the control group, the PR per cycle and per ET were 12.1% (4 of 33) and 14.3% (4 of 28), respectively. Statistically significant differences were found between the two groups in the PR per cycle (P=.02) and PR per ET (P=.03). No statistically significant difference was found between the groups for the stage in which the embryos were cryopreserved, the survival cleavage rates after thawing, grading of thawed embryos, and number of embryos transferred. CONCLUSION(S): In couples with unexplained infertility, the PR may be improved by combining IUI and FT-ET with ovulation induction. Performing IUI before thawing may prevent treatment cancellation in cycles with no surviving embryos.