Israel Medical Association Journal

Background: Omega-3 fatty acids promote fertility in males and females and constitute an important factor in the normal development of the fetus.

Objectives: We investigated the effect of omega-3 supplements during ovulation induction treatment in women with polycystic ovary syndrome (PCOS)-related infertility.

Methods: A randomized, double-blind study was conducted for 60 treatment cycles in 34 women with PCOS-related oligo/anovulation referred to the fertility clinic at the Bikur Cholim/Shaare Zedek Medical Center in Jerusalem, who underwent ovulation induction with clomiphene citrate (50 mg). Seventeen women (mean age 33.9 ± 0.9 years) received omega-3 supplements (3 × 600 mg/day) and 17 received placebo capsules (mean age 32.7 ± 0.9 years) for a maximum of two cycles. We recorded their characteristics and data from their serial hormonal blood tests and ultrasound examinations. We also conducted both univariate and multivariate analyses. The primary endpoint was conception.

Results: There were clinical pregnancies in 8/30 (26.7%) treatment cycles for women receiving omega-3 supplements versus 4/30 (13.3%) cycles with placebo. Among overweight/obese women (body mass index [BMI] 25–35), there were clinical pregnancies in 8/27 cycles (29.6%) versus 1/19 (5.3%) with placebo (P < 0.04). For overweight/obese PCOS women, omega-3, lower BMI rates, and higher values of the endometrium’s thickness increased the odds of becoming pregnant. No harmful side effects from the omega-3 treatment were reported.

Conclusions: Omega-3 supplements demonstrated beneficial effects for fertility in women diagnosed with PCOS. Among the overweight/obese participants, the increased clinical pregnancy rate was significant.

Background: Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often advised prior to radical orchiectomy. However, whether affected testes contribute to fertility is unclear.

Objectives: To determine whether maximal tumor diameter (MTD) is correlated with ipsilateral fertility (IF) in patients treated for GCT.

Methods: We reviewed medical charts for demographic and clinical data of patients with GCT who had undergone orchiectomy at our institution between 1999 and 2015. The extent of spermatogenesis was categorized into three groups: full spermatogenesis, hypospermatogenesis, and absence of spermatogenesis. The presence of mature spermatozoa in the epididymis tail was also assessed. We defined IF as the combination of full spermatogenesis in more than 100 tubules and the presence of mature spermatozoa in the epididymis tail. Mann–Whitney was applied to determine the correlation between MTD and IF.

Results: Of 57 patients, IF was present in 28 (49%). Mean patient age was 32.8 years in patients with positive IF and 33.4 years those with negative IF. Seminoma was diagnosed in 46.4% of patients with positive IF and in 65.5% of patients with negative IF. Full spermatogenesis was observed in 33 patients (57.8%). In 48 (82.7%), mature epididymal spermatozoa were found. No correlation was found between MTD and IF.

Conclusions: IF is present in almost half of the patients undergoing radical orchiectomy. Because IF cannot be predicted by MTD, routine pre-orchiectomy sperm banking is suggested.

Background: Laparoscopic salpingectomy is strongly related to successful in vitro fertilization (IVF) treatments.

Objectives: To compare the ovarian reserve, including anti-mullerian hormone (AMH) levels, in patients who underwent salpingectomy before IVF to IVF patients who had not been salpingectomized.

Methods: In this retrospective study, medical records of women who were treated by the IVF unit at our institute were reviewed. We retrieved demographic data, surgical details, and data regarding the ovarian reserve. Details of 35 patients who were treated by IVF after salpingectomy were compared to 70 IVF patients with no history of salpingectomy treatment. Nine women underwent IVF treatment before and after having salpingectomy, and their details were included in both groups.

Results: The levels of AMH, follicular stimulating hormone (FSH), estradiol, and progesterone were not significantly different in the groups. The antral follicular count (AFC), number of oocytes retrieved, amount of gonadotropin administered for ovarian stimulation, and number of embryos transferred (ET) were also not significantly different.

Conclusions: Salpingectomy does not seem to affect ovarian reserve in IVF patients.

Background: Male infertility is solely responsible for approximately 20% of all infertility in couples. Various factors have been proposed as having a negative effect on sperm quality; however, the reasons for the global decline in sperm parameters during the last few decades are still controversial. 

Objectives: To investigate the fluctuations of semen parameters (sperm concentration, motility, and morphology) in three sperm quality groups and to examine the trends of those parameters in the same men over time. 

Results: Our data showed deterioration in all semen parameters assessed in the group of men originally considered as having normal semen values according to the 2010 criteria of the World Health Organization. In contrast, we found significant improvement over time in all semen parameters in the group of men with severe oligo-terato-asthenozoospermia. 

Conclusions: Our results suggest that, although there were changes in sperm quality over time in the groups assessed, the clinical significance is negligible and does not necessarily justify a change in the therapeutic approach to infertility or sperm cryopreservation. 

 

Background: Controlled ovarian hyperstimulation (COH) followed by oocyte retrieval is a leading option for fertility preservation before chemotherapy, yet this procedure causes excessive serum levels of estradiol (E2), which are often detrimental for cancer patients. Aromatase inhibitors are often used in breast cancer patients during COH to prevent elevated levels of E2.

Objectives: To describe our experience with COH for oocyte cryopreservation in non-breast cancer patients using aromatase inhibitors.

Methods: Of the five patients treated, two had an aggressive abdominal desmoid tumor, one had endometrial carcinoma, one had uterine sarcoma, and one patient had a brain oligodendroglioma. In all cases the treating oncologist suggested an association between estrogen and possible tumor progression. All patients were treated with a standard in vitro fertilization antagonist protocol combined with aromatase inhibitors, similar to the protocol used for breast cancer patients.

Results: The average duration of treatment was 10.5 days, mean peak E2 was 2348 pmol/L, mean number of oocytes aspirated was 17.3, and a mean of 14.6 embryos/oocytes were cryopreserved.

Conclusions: COH with aromatase inhibitors is apparently effective in non-breast cancer patients and spares exposure to high E2 levels.

Background: Despite the large volume of evidence on the management of retained products of conception (RPOC), there are virtually no data regarding the optimal time frame of surgical intervention in case of RPOC.

Objectives: To examine whether the time interval between spontaneous vaginal delivery or pregnancy termination and the uterine evacuation due to pathologically confirmed RPOC influences the reproductive outcome.

Methods: We retrospectively reviewed all the records of women who were admitted to our department due to pathologically confirmed RPOC following either spontaneous vaginal delivery or pregnancy termination between January 2000 and December 2010. Based on the median time from delivery or pregnancy termination until the operative intervention in the study group, patients were stratified into two groups: early intervention (< 3 weeks) and late intervention (> 3 weeks). Reproductive outcomes were compared between the two study groups. 

Results: Reproductive outcomes were analyzed in 172 patients with pathologically confirmed RPOC. Of them, 95 (55.2%) were included in the early intervention group and 77 (44.8%) in the late intervention group. There were no significant differences in the conception rate, mean time to conception, and the occurrence rate of a new infertility problem in women with early surgical intervention compared to those with late surgical intervention (P > 0.05). Furthermore, there was no significant difference between the groups in the pregnancy outcomes following RPOC. 

Conclusions: Early surgical intervention in women with pathologically confirmed RPOC following spontaneous vaginal delivery or pregnancy termination yields the same reproductive outcomes as late surgical intervention.

 

Background: Antiphospholipid antibodies (aPL) have been advocated as potential mediators of unexplained female infertility, but no evidence has yet been raised to support such an association.

Objectives: To test the hypothesis that aPL might interfere with uterine decidualization, a gene expression study was performed on decidual stromal cells treated with different aPL preparations.

Methods: Decidual stromal cells were isolated from first-trimester deciduas obtained from two women undergoing elective abortion, and treated with: (i) a β2GPI-dependent aPL monoclonal antibody (IS3); (ii) IS3 plus TIFI, a synthetic peptide mimicking PL-binding region of β2GPI; and (iii) IgG from healthy subjects (NHS). Gene expression data were acquired using human HT-12 v3 beadchip arrays (Illumina). Differential expression analysis was performed by fitting a gene-wise linear model using the treatment group and decidual source as covariates.

Results: In the comparison of IS3 versus IgG NHS-treated decidual cells, gene ontology (GO) enrichment was expressed in terms relating to well-characterized aPL-mediated cellular effects: “inflammatory response,” “immune response,” “response to stress,” “oxydoreductase activity,” “metalloendopeptidase activity,” and “cytokine/chemokine activity.” As expected, almost all genes were up-regulated by IS3 treatment. The same GO categories appeared to be differentially expressed when IS3 treatment was compared to IS3 + TIFI, but with most genes being down-regulated.

Conclusions: Given the inflammatory response evinced at gene expression analysis on decidual stromal cells treated with a β2GPI -dependent aPL monoclonal antibody, it is feasible that aPL might interfere with uterine decidualization, affecting the early stages of implantation and ultimately resulting in female infertility.

 

Autoimmune rheumatic diseases (ARD) affect mainly young women during their reproductive years. Fertility is usually not diminished but the time it takes to conceive is usually longer. Factors related to an ARD or to its treatment are responsible for this effect. In addition, contraception counseling is required to prevent negative fetal outcome and exacerbation of disease symptoms. In recent years, advances in therapies, clarification of risk factors for adverse pregnancy outcomes, and a multidisciplinary approach have vastly improved obstetric management, increasing the possibility of successful pregnancy with a high likelihood of favorable outcome.

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Background: Infertility is one of the most prevalent health disorders in young adults.

Objectives: To study the distribution of causes of infertility in couples referred to primary infertility clinics in Israel.

Methods: Data for a 9 year period were derived from two clinics of major women's hospitals run by the country's largest health insurance funds. All patients were treated by one physician. Laparoscopy was not performed to rule out endometriosis.

Results: Of the 2515 couples identified, 1991 (79.2%) had a definitive diagnosis following complete workup (including hysterosalpingography). Mean age was 29.6 ± 6.0 years; mean duration of infertility was 1.7 ± 1.8 years. Primary infertility accounted for 65% of cases. Causes of infertility were male factor (45%), oligo-ovulation disorders (37%), and tubal damage (18%). Infertility factors were identified in the woman alone in 30.6% of cases and the man alone in 29.2%. Two combined infertility factors were found in 18% of patients, and three combined factors in 0.5%. The rate of unexplained infertility (which probably includes non-tubal endometriosis) was 20.7%.

Conclusions: As male factor accounts for almost half of all cases of infertility in couples, sperm analysis is mandatory before any treatment.