Pre-implantation genetic diagnosis-should we use ICSI for all?

OBJECTIVE: Intracytoplasmic sperm injection (ICSI) is commonly used during pre-implantation genetic diagnosis (PGD) in vitro fertilization (IVF), aiming to eliminate the risk of contamination from extraneous sperm DNA. Recently, ICSI "overuse" in non-male infertility has been doubted, since it does not offer an advantage over IVF. Prompted by the aforementioned observations, we sought to assess the accuracy of IVF vs ICSI in PGD cases, as might be reflected by a difference in the prevalence of discarded embryos as a consequent of parental contamination. METHODS: Cohort-historical study of all consecutive patients admitted to the IVF-PGD program in a large tertiary center. The percentages of complete, incomplete diagnosis, PCR failure, abnormal embryos, and the contamination rate with paternal DNA in the IVF-only and the ICSI-only groups. We reviewed the computerized files of all consecutive women admitted to our IVF for a PGD-PCR cycle. Patients were divided accordingly into three groups: an IVF group-where all the oocytes underwent IVF only, an ICSI group-where all oocytes underwent ICSI, and a mixed group-where sibling oocytes underwent both IVF and ICSI. The laboratory data and the genetic diagnostic results were collected and compared between the different insemination groups. RESULTS: Nine-hundred and twenty-seven patients underwent IVF-PGD cycles in our program, 315 in the IVF group, 565 in the ICSI group, and 47 in the mixed group. No differences were observed in fertilization rates, the percentage of embryos available for biopsy, and the percentages of complete, incomplete diagnosis, PCR failure, or abnormal embryos, between the IVF-only and the ICSI-only groups and between the IVF and the ICSI of sibling oocytes in the mixed group. Moreover, contamination with paternal DNA, through contamination with sperm cells, was negligible. Not one single case of misdiagnosis was encountered during the study period. CONCLUSION: It might be therefore concluded that IVF should be the preferred insemination methods in PGD cycles, and ICSI should be indicated only in cases of male-factor infertility.

Pregnancy outcomes in oocyte recipients with fibroids not impinging uterine cavity.

OBJECTIVE: To examine the effects of fibroid uterus on pregnancy outcomes and endometrial features in ovum donation recipients. METHODS: Retrospective analysis of 744 ovum donation cycles was conducted in two private IVF centers between 2005 and 2012. All the recipients underwent transvaginal ultrasound examination, including endometrial thickness and grade measurements. Clinical pregnancy, spontaneous miscarriage, and live birth rates were regarded as the primary outcomes. RESULTS: Leimyomas not distorting the uterine cavity were diagnosed in 264 (35.5%) of the cycles. This group exhibited lower endometrial thickness (8.33 ± 1.8 vs. 8.73 ± 2.03 mm, p = 0.009), lower rates of Grade A (16.1 vs. 30.1%, p < 0.0001), and higher rates of grade C endometrium (10.2 vs. 5.5%, p < 0.0001), compared to the group with sonographically normal uterine cavity. In addition, significantly higher spontaneous miscarriage rates were found in fibroid uteri group (25 vs. 14.5%, p = 0.036). CONCLUSION: Our study results suggest that uterine fibroids not distorting the uterine cavity could constitute a risk factor for spontaneous miscarriage in oocyte donation cycles, possibly via their adverse effect on endometrial receptivity. Further well-designed trials should widely explore this subject, particularly focusing on impact of myomectomy on fertility rates in these patients.

Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles.

OBJECTIVE: To evaluate the effect of local endometrial injury (LEI) on clinical outcomes in ovum donation recipients. DESIGN: Retrospective cohort analysis of ovum donation cycles conducted from 2005 to 2012. SETTING: Two private IVF centers. PATIENT(S): Total 737 ovum donation cycles. INTERVENTION(S): LEI by endometrial "scratch" with the use of a Pipelle catheter. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth rates. RESULT(S): No statistically significant differences were found in clinical pregnancy rates and live birth rates in cycles subjected to LEI compared with those without. Combination of LEI with fibroid uterus resulted with significantly higher clinical pregnancy rates compared with LEI in normal uterine anatomy. CONCLUSION(S): This is the first study done in ovum recipients who underwent LEI by a "scratch" procedure after failed implantation. Unlike most previous reports, which found improved pregnancy rates with the use of "scratch effect" or "minor endometrial injury" after repeated implantation failures in standard IVF with own eggs, we did not find any changes in implantation rates in a population of egg recipients following this procedure. In view of a possible positive effect of LEI in cycles with a previous four or more failures, prospective randomized controlled studies are warranted to better define the target population who may benefit from this intervention.

Tamoxifen co-administration during controlled ovarian hyperstimulation for in vitro fertilization in breast cancer patients increases the safety of fertility-preservation treatment strategies.

OBJECTIVE: To evaluate the safety and efficacy of tamoxifen co-administration during conventional controlled ovarian hyperstimulation (COH) protocols for a fertility-preservation IVF cycle in breast cancer patients. DESIGN: Two groups: retrospective descriptive cohort study and prospective study. SETTING: Breast cancer oncology and fertility-preservation centers in a tertiary hospital. PATIENT(S): Two groups of breast cancer patients: premenopausal patients treated with adjuvant tamoxifen; and patients undergoing in vitro fertilization (IVF) for fertility preservation. INTERVENTION(S): Fertility-preservation cycles, tamoxifen co-administration during conventional IVF. MAIN OUTCOME MEASURE(S): Endocrine records, and IVF results. RESULT(S): Estradiol (E2) levels were chronically high (mean 2663 pmol/L, maximum: 10,000 pmol/L) in 38 of 46 breast cancer patients treated with adjuvant tamoxifen. Co-administration of tamoxifen (48 cycles) during conventional IVF or without tamoxifen (26 cycles), using either the long gonadotropin-releasing hormone-agonist or-antagonist protocols, resulted, respectively, in a mean of 12.65 and 10.2 oocytes retrieved, and 8.5 and 6.4 embryos cryopreserved. Average peak E2 levels were 6,924 pmol/L and 5,093 pmol/L, respectively, but long-term recurrence risk (up to 10 years) was not increased. CONCLUSION(S): In breast cancer patients, co-administration of tamoxifen during conventional COH for fertility preservation does not interfere with IVF results. The high serum E2 levels during COH should be considered safe, as it simulates the high prevalence of persistently high serum E2 levels in premenopausal breast cancer patients safely treated with adjuvant tamoxifen.

Comparison between two protocols for thawed embryo transfer: natural cycle versus exogenous hormone replacement.

INTRODUCTION: There are two most popular protocols for Frozen Embryo Transfer: the natural and the E2&P4 replacement cycles. There is still a controversy whether one is superior over the other. PURPOSE: To compare the outcome in patient groups undergoing FET following these protocols. METHODS: About 1235 FET cycles were retrospectively analyzed during a period of 12 years. In 798 cycles (group A), the natural cycle protocol was used, and in 437 cycles (group B), the exogenous E2&P4 administration protocol was used. RESULTS: The average patient age was 32.11 ± 0.27 years in group A and 32.94 ± 0.19 years in group B (p<0.05). The endometrial thickness was 9.54 ± 0.11 mm and 8.95 ± 0.13 mm in groups A and B, respectively (p<0.001). The peak serum E2 level was 162.51 ± 8.97 pg/mL and 250.78 ± 33.67 pg/mL in groups A and B, respectively (p<0.001). The implantation, clinical pregnancy, and ongoing pregnancy rates in groups A and B were 6.47%, 12.91%, and 10.4% versus 4.26%, 8.47%, and 5.95%, respectively (p<0.05). CONCLUSIONS: Natural endometrial preparation yields better outcome in compare with exogenous E2&P4 in FET cycles with higher endometrial thickness, implantation, and clinical pregnancy rates.

Thin endometrium in donor oocyte recipients: enigma or obstacle for implantation?

OBJECTIVE: To evaluate the combined effect of endometrial thickness and anatomic uterine factors on clinical outcome in oocyte donation recipients. DESIGN: Retrospective analysis of oocyte donation cycles conducted between 2005 and 2010. SETTING: Two private IVF centers. PATIENT(S): A total of 737 donor oocyte cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth rates. RESULT(S): No statistically significant difference was found in clinical pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm compared with those with endometrial thickness >10 mm. However, a relatively high rate of live births was found within a medium range of endometrial thickness (8.2-10 mm). All intrauterine adhesion cases occurred in cycles with thinner endometrium. CONCLUSION(S): No statistically significant difference was found in clinical pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm compared with those with thickness >6 mm. A relatively high rate of live births was found within a medium range of endometrial thickness (9.1-10 mm).

Male infertility associated with adult dominant polycystic kidney disease: a case series.

INTRODUCTION: Although described earlier, the association of male infertility with adult dominant polycystic kidney disease (ADPKD) is quite rare and unfamiliar to some of the multidisciplinary team members caring for affected men. MATERIALS AND METHODS: Infertile men diagnosed to have ADPKD were evaluated by clinical characteristics including testis volume, as well as serum hormone levels, semen analysis, and transrectal ultrasonography (TRUS) because of low volume ejaculate. RESULTS: Semen analysis revealed low-normal volume, normal pH, and azoospermia/virtual azoospermia. Serum hormones were within the normal range. Transrectal ultrasonography demonstrated cystic dilatation of the seminal vesicles in all three men. CONCLUSION: Patients should be referred for andrological evaluation of a presentation similar to obstructive azoospermia. Their potential to achieve paternity by surgical sperm retrieval combined with assisted reproductive technology is another example of cooperation between andrologists and gynecologists.

Ovarian tissue cryopreservation in hematologic malignancy: ten years' experience.

Cryopreservation of ovarian tissue is currently practiced in an attempt to preserve fertility before commencing potentially sterilizing chemotherapy. Clinical and laboratory guidelines are needed to standardize the procedure. Over the last 10 years ovarian tissue was stored in female patients with hematologic malignancies. Patients' records and consultation charts were evaluated, surgical and laboratory reports were revised and ovarian histology was investigated. Fifty-six patients with hematologic malignancies (age 24 +/- 5.5) had cryopreserved ovarian tissue. Thirty-three patients had Hodgkin's disease, 14 non-Hodgkin's lymphoma, 6 acute leukemia, and 3 chronic myelocytic leukemia. Harvesting of ovarian tissue was also performed following previous exposure to chemotherapy (33 patients), 13 of them shortly after the chemotherapy. Partial oophorectomy was the preferred surgical procedure. Fertility was restored with ovarian tissue transplantation in a sterilized patient and following fertility treatment in a patient with very low ovarian reserve. We recommend that indications and timing of ovarian tissue banking should be individualized. Patients previously exposed to chemotherapy can consider ovarian tissue freezing. The extent of tissue removed should take into account the large number of follicles lost and the risk of future sterilization. Tissue handling should enable further investigation of primordial follicles and identification of cancer cells.

Monitoring the ovaries after autotransplantation of cryopreserved ovarian tissue: endocrine studies, in vitro fertilization cycles, and live birth.

OBJECTIVE: To investigate fertility potential of ovarian tissue harvested after chemotherapy, to monitor ovarian recovery after transplantation, and to compare with in vitro fertilization (IVF) cycles. DESIGN: Clinical and endocrine study. SETTING: IVF unit and hematology department in a tertiary university hospital. PATIENT(S): A 28-year-old patient suffering from non-Hodgkin's lymphoma had some of her ovarian tissue cryopreserved shortly after conventional chemotherapy and failure to respond to ovarian stimulation but before sterilizing treatment. INTERVENTION(S): Transplantation of cryopreserved ovarian tissue; four IVF cycles. MAIN OUTCOME MEASURE(S): Gonadotropins, ovarian steroids, anti-Mullerian hormone (AMH), inhibin B, ovarian histology, sonography, and outcome of IVF cycles. RESULT(S): Large number of primordial follicles were present in the harvested tissue. During the first months after transplantation, gonadotropins were high, AMH and inhibin B were low, and in three IVF cycles, eggs were not found. After recovery of endocrine activity 9 months after transplantation, a mature oocyte was retrieved. Embryo transfer resulted in a normal pregnancy and delivery of a healthy baby. Although spontaneous menstruation resumed after delivery, endocrine profile 22 months after transplantation indicated low reserve. CONCLUSION(S): The recovery of endocrine function after transplantation correlated with the result of oocyte recovery. Fertility preservation using ovarian tissue is effective also in cases when the ovaries are injured after chemotherapy. However, transplant life span is limited.

Role of transrectal ultrasonography in the evaluation of azoospermic men with low-volume ejaculate.

OBJECTIVE: The purpose of this prospective study was to evaluate the incidence of distal ejaculatory system defects with transrectal ultrasonography (TRUS) among patients evaluated for azoospermia. METHODS: Forty-two patients with low-volume ejaculate and azoospermia were evaluated by physical examination, serum follicle-stimulating hormone and luteinizing hormone level determination, karyotyping, selective screening for cystic fibrosis mutations, and TRUS. RESULTS: On physical examination, in 29 patients (69%), either 1 (12 patients) or both (17 patients) of the vasa deferentia could not be palpated. In the group of 17 patients with bilateral involvement of the vasa deferentia, the ultrasonographic imaging universally showed bilateral absence or hypoplasia of the seminal vesicles with bilateral agenesis of the vasa deferentia and nonvisualization of both ejaculatory ducts. In the patients with a unilateral abnormality on physical examination, the ultrasonographic imaging showed absence of the ipsilateral seminal vesicle in 7 patients and the hypoplastic seminal vesicle in 5. In the group of 13 patients with normal physical examination findings, a variety of obstructive causes were diagnosed by TRUS examination. CONCLUSIONS: According to this study, TRUS appears to be a sensitive method for evaluating the anatomy of the distal ejaculatory system. Its safety and low costs make it a good alternative to the other invasive and expensive methods.

Effects of intravesical chemotherapy and immunotherapy on semen analysis.

OBJECTIVES: To study the effect of intravesical chemo-immunotherapy on the sperm parameters of young patients. METHODS: Twelve young male patients with superficial transitional cell carcinoma, all younger than 40 years old at surgery, were included in this prospective study. The mean patient age was 34.8 years (range 22 to 40). Of the 12 patients, 8 had superficial transitional cell carcinoma, grade 2-3, and 4 had proven invasion to the lamina propria; 1 patient had accompanying carcinoma in situ. Accordingly, adjuvant intravesical treatment with either bacille Calmette-Guérin (BCG; 6 patients) or mitomycin C (6 patients) was indicated on the basis of the initial stage and grade. Sperm analysis was performed before bladder irrigation and subsequently 3 months after completion of intravesical therapy. RESULTS: All 12 patients had normal follicle-stimulating hormone and luteinizing hormone levels after surgery. All 12 patients had normal-volume ejaculate, except for 1 who had undergone multiple prior transurethral tumor resections. Of the 6 patients who were treated with mitomycin C, only a few minor insignificant changes in the sperm quality were noted, and 2 of them later fathered healthy children. However, in 3 of the BCG-treated patients, remarkable changes in all sperm quality parameters were evident, with a statistically significant decrease in the sperm count (P = 0.0021). CONCLUSIONS: We suggest that potential adverse effects on spermatogenesis can be induced by intravesical therapy with BCG and that, consequently, routine pretreatment semen preservation should be considered as a precaution before instillation of intravesical BCG to prevent subsequent fertility difficulties in young men.