Intraovarian platelet-rich plasma injection and IVF outcomes in patients with poor ovarian response: a double-blind randomized controlled trial.

STUDY QUESTION: Does platelet-rich plasma (PRP) intraovarian injection increase the number of retrieved oocytes in successive ovarian punctions among patients with poor ovarian reserve (POR)? SUMMARY ANSWER: The injection of PRP increases the number of retrieved oocytes without increasing the quality of developed blastocysts. WHAT IS KNOWN ALREADY: Management of women with reduced ovarian response to stimulation is one of the significant challenges in reproductive medicine. Recently, PRP treatment has been proposed as an adjunct in assisted reproduction technology, with controversial results. STUDY DESIGN, SIZE, DURATION: This placebo-controlled, double-blind, randomized trial included 60 patients with POR stratified according to the POSEIDON classification groups 3 and 4. It was conducted to explore the efficacy and safety of intraovarian PRP injection. Patients were proposed to undergo three consecutive ovarian stimulations to accumulate oocytes and were randomized to receive either PRP or placebo during their first oocyte retrieval. Randomization was performed using computer-generated randomization codes. Double blinding was ensured so that neither the participant nor the investigators knew of the treatment allotted. All patients underwent three ovarian stimulations and egg retrieval procedures. ICSI was performed after a third ovarian puncture. The primary endpoint was the number of mature oocytes retrieved after PRP or placebo injection in successive ovarian punctures. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty women (30-42 years) fulfilling inclusion criteria were randomized in equal proportions to the treatment or control groups. MAIN RESULTS AND THE ROLE OF CHANCE: The baseline demographic and clinical characteristics [age, BMI, anti-Müllerian hormone (AMH) levels] were comparable between the groups. Regarding the primary endpoint, the cumulative number (mean ± SEM) of retrieved mature oocytes was slightly higher in the treatment group: 10.45 ± 0.41 versus 8.91 ± 0.39 in the control group, respectively (95% CI of the difference 0.42-2.66; P = 0,008). The number of mature oocytes obtained among all patients increased in successive egg retrievals: 2.61 ± 0.33 (mean ± SEM) in punction 1 (P1), 3.85 ± 0.42 in P2, and 4.73 ± 0.44 in P3. However, the increase was higher among patients receiving the assessed PRP treatment. In P2, the number of retrieved mature oocytes was 4.18 ± 0.58 versus 3.27 ± 0.61 in controls (95% CI of the difference: -0.30 to 2.12; P = 0.138) and in P3, 5.27 ± 0.73 versus 4.15 ± 0.45 (95% CI of the difference: 0.12-2.12; P = 0.029). The mean ± SEM number of developed and biopsied blastocysts was 2.43 ± 0.60 in the control group and 1.90 ± 0.32 in the treatment group, respectively (P = 0.449). The mean number of euploid blastocysts was 0.81 ± 0.24 and 0.81 ± 0.25 in the control and treatment groups, respectively (P = 1.000). The percentages of patients with euploid blastocysts were 53.33% (16 out of 30) and 43.33% (13 out of 30) for patients in the control and treatment groups, respectively (Fisher's exact test P = 0.606). The overall pregnancy rate per ITT was 43% (26 out of 60 patients). However, the percentage of clinical pregnancies was higher in the control group (18 out of 30, 60%) than in the treatment group (8 out of 30, 27%) (P = 0.018). There was also a trend toward poorer outcomes in the treatment group when considering full-term pregnancies (P = 0.170). There were no differences between control and treatment groups regarding type of delivery, and sex of newborns. LIMITATIONS, REASONS FOR CAUTION: The mechanism of the potential beneficial effect of PRP injection on the number of retrieved oocytes is unknown. Either delivered platelet factors or a mechanical effect could be implicated. Further studies will be needed to confirm or refute the data presented in this trial and to specify the exact mechanism of action, if any, of PRP preparations. WIDER IMPLICATIONS OF THE FINDINGS: The increasing number of women with a poor response to ovarian stimulation supports the exploration of new areas of research to know the potential benefits of therapies capable of increasing the number of oocytes available for fertilization and improving the quality of developed blastocysts. An increase in the retrieved oocytes in both arms of the trial suggests that, beyond the release of growth factor from platelets, a mechanical effect can play a role. However, neither improvement in euploid blastocyst development nor pregnancy rates have been demonstrated. STUDY FUNDING/COMPETING INTEREST(S): This trial was supported by Basque Government and included in HAZITEK program, framed in the new Euskadi 2030 Science and Technology Plan (PCTI 2030). These aids are co-financed by the European Regional Development Fund (FEDER). The study funders had no role in the study design, implementation, analysis, manuscript preparation, or decision to submit this article for publication. No competing interests are declared by all the authors. TRIAL REGISTRATION NUMBER: Clinical Trial Number EudraCT 2020-000247-32. TRIAL REGISTRATION DATE: 3 November 2020. DATE OF FIRST PATIENT'S ENROLLMENT: 16 January 2021.

Correlation between plasmatic progesterone, endometrial receptivity genetic assay and implantation rates in frozen-thawed transferred euploid embryos. A multivariate analysis.

OBJECTIVE: To ascertain the predictive value of different parameters to determine endometrial receptivity among assisted reproduction treatments in which single embryo transfer of frozen-thawed euploid blastocysts are performed. STUDY DESIGN: Observational study involving 104 patients recruited between September.2018 and June.2019 at a University associated assisted reproduction center. The relationship of different parameters (age, body mass index (BMI), duration of hormonal preparation, plasmatic progesterone levels, endometrial parameters at ultrasound assessment and endometrial receptivity determined by endometrial receptivity assay (ERA) was evaluated by a multivariable logistic (binomial) analysis after hormonal preparation. According to the ERA test results a personalized endometrial transfer (pET) was scheduled and live birth rate was assessed. Only single transfers of frozen euploid blastocysts were performed. RESULTS: ERA test report predicted receptive endometrium (RE) in 54,64% patients and non-receptive (NR) in 45,31% patients. Among NR endometrial samples, 20,62% were classified as pre-receptive or early receptive, whereas 24,74% as post-receptive or late-receptive. The univariate analysis showed a relationship between BMI, doses of progesterone administered before biopsy and the receptivity of endometrium. There was no relationship between age of women, duration of hormonal supplementation, and the results of ERA test. In our series, endometrial receptivity was not related neither to endometrial thickness nor plasmatic progesterone levels. The multivariate analysis showed that both, BMI and cumulative progesterone administered prior to the test are independent predictive factors of endometrial receptivity (p = 0,047 and p = 0,034 respectively). The overall live birth rate after FET of euploid embryos was 62,35%. The odd of pregnancy was higher when ERA test was performed prior to the first embryo transfer (93,10% vs. 46,43%; OR = 15,58;95%CI 3,38-71,89). Overall, ongoing pregnancy rates showed a favorable trend after "non-receptive" endometria had been diagnosed and, thus, a modified (pET) preparation was performed (70,00% vs. 55,56%; OR = 1,87; 95% CI 0,76-4,57). CONCLUSION: Regarding implantation potential of genetically screened blastocysts, the traditional tools used for assessing endometrial receptivity such as transvaginal evaluation of endometrial thickness and pattern or progesterone levels determination were not useful among our patients for predicting a receptive endometrium.

Chemotherapy-induced emesis: management of early and delayed emesis in milder emetogenic regimens.

The objective of the present study was to examine the problem of the control of nausea and vomiting induced by non-cisplatin containing cyclophosphamide-based chemotherapy regimens in breast cancer patients. This was randomized, double-blind, parallel-group and placebo-controlled study comparing the efficacy of three antiemetic therapeutic regimens (ondansetron for 3 days, ondasetron plus metoclopramide, and ondansetron given in a single dose) in breast cancer patients receiving cyclophosphamide-based chemotherapy regimens on an outpatient basis. Both the primary and the secondary efficacy were measured. The primary efficacy variable was the number of emetic episodes (considering early and delayed emesis). The secondary efficacy variable measured was the quality of life. Two-by-two tables using the chi-square test and relative-risk concept were elaborated for statistical analysis. There was no difference between high-dose ondansetron and ondansetron plus metoclopramide among patients given CMF (cyclophosphamide, methotrexate, 5-fluorouracil). The single-dose ondansetron regimen showed the worst results. In patients given an FEC regimen (cyclophosphamide, epirubicin, 5-fluorouracil) the antiemetic efficacy was best for the high-dose ondansetron regimen, followed by the ondansetron plus metoclopramide regimen, and was worst for single-dose ondansetron administration. Despite the use of different antiemetic schedules, nausea and emesis are significant problems in patients receiving cyclophosphamide-based chemotherapy. Their adequate control should be the aim of any antiemetic approach.

Angiosarcoma of the breast and pregnancy: a new therapeutic approach.

A case of angiosarcoma of the breast managed primarily by a chemotherapeutic approach is referred. A 29-year-old patient presented complaining of a painful mass in her right breast. An incisional biopsy carried out under general anesthesia showed a moderately-differentiated angiosarcoma surrounded by fibrofatty tissue. Ruled out distant metastases, a decision was made to initiate neoadjuvant chemotherapy consisting of ifosfamide, vincristine and dactinimycin. After 2 courses of chemotherapy the tumor volume was reduced by 50% and the histologic examination of the mastectomy specimen revealed a well-differentiated angiosarcoma with widespread areas of necrosis probably produced by previous chemotherapic treatment. The patient is clinically free of disease after 24 months of follow-up. Although this is a single case report, and by no means can be considered a guideline for future treatments, we nevertheless feel that the result obtained with the chemotherapeutic approach with this patient is encouraging.

Pruritic urticarial papules and plaques of pregnancy.

The authors present a rare case of pruritic urticarial papules and plaques of pregnancy in a 25-year-old caucasian primigravida admitted to our department because of pruritus in the third trimester of gestation. Recommendations for management are discussed.

Abdominal mass in a young woman. Pitfalls and delayed diagnosis. Case report.

Although germ cell tumors arising from adnexa are relatively frequent among young women, diagnosis is often delayed by omitting basic diagnostic procedures. This case report highlights the importance of using the available diagnostic tools beginning from the simplest one, i.e., physical examination, to the most sophisticated and reliable one (ultrasonography). Diagnostic pitfalls and management of a massive ovarian tumor in an 18 year-old woman are reported.

The role of second look laparotomy and tumor markers in the follow-up of endodermal sinus tumor of the ovary. A case report and review of the literature.

Endodermal sinus tumor (EST) of the ovary is extremely rare and little information exists about therapy and the role of second-look laparotomy in the management of this entity. A case of EST of the ovary in a 21 year old woman is reported. She received conservative surgery and six courses of combination therapy consisting of Vincristine, Actinomycin D and Cyclophosphamide before second-look laparotomy. Due to progression of the disease second-line polychemotherapy with Vinblastine, Bleomycin and Cisplatin was administered. This new regimen reduced the alpha-fetoprotein to normal levels although the patient was not free of disease on second-look laparotomy. Precise guidelines for the management of this disease, especially in advanced stages, are still lacking.

Pure theca cell tumors. A clinicopathologic study of 29 cases.

From 1976 to 1989, 29 cases of ovarian theca cell tumors were diagnosed at the Pathology Department of our Hospital. Their clinical and histologic features were reviewed. The main presenting symptom in postmenopausal patients was uterine bleeding, whereas in premenopausal women, abdominal swelling and the findings of ultrasonographic examination were the diagnostic keys. Different surgical procedures were the cornestone of treatment, although in 12 cases the indication for surgery was not apparently related to an adnexal condition.

Serum CA 125, CA 15.3 and CA 19.9 levels and surgical findings in patients undergoing second look operations for ovarian carcinomas.

Sera from 52 ovarian cancer patients undergoing chemotherapy and second look operation were studied. CA 125, CA 15.3 and CA 19.9 assays were performed during chemotherapy and prior to relaparotomy. Twenty-six patients (50%) had no evidence of disease whereas 2 (3.8%) and 24 (46.1%) had microscopic and macroscopic disease. In general although the predictive value of an elevated CA 125 or CA 15.3 level is excellent, a normal value (less than 35 U/ml) has limited significance. Moreover, we found no improvement in negative predictive and positive predictive value by adding the determination of CA 19.9.

[Involvement of histocompatibility and allosensitization in recurrent abortions]. / Implicación de la histocompatibilidad y la alosensibilización en los abortos de repetición.

BACKGROUND: The aim of this study was to know the possible implication of human histocompatibility (HLA) antigens in the etiology of repeated abortions. METHODS: Antigen typing for the major histocompatibility system was carried out in 65 couples with 2 or more abortions and comparative analysis was performed with 40 fertile couples by the odds ratio. Likewise, the possible relationship between cytotoxic antibodies in maternal serum and reproductive prognosis was determined. RESULTS: The couples with abortions did not present a significantly different phenotypic frequency from that of the fertile couples in regard to the HLA antigens (loci HLA-A, HLA-B, and HLA-DR). On considering the 3 loci studied, the infertile couples presented significantly higher antigenic HLA identity than the fertile couples. This significance was demonstrable both by association and by odds ratio (OR: 4.9; CI 95%; 1.1-9.2). No differences were observed among women with primary (no full term pregnancy) or secondary abortions (some full term pregnancies) with regard to common HLA antigens, with both groups being homogeneous. CONCLUSIONS: The presence of cytotoxic antibodies against paternal lymphocytes in maternal serum detected by cross-match reaction was not related to the pertaining to an infertile (including any of the established subgroups) or fertile population. Neither were differences observed in the presence of these antibodies among women with primary or secondary abortions.

Stream temperature response to three riparian vegetation scenarios by use of a distributed temperature validated model.

Elevated in-stream temperature has led to a surge in the occurrence of parasitic intrusion proliferative kidney disease and has resulted in fish kills throughout Switzerland's waterways. Data from distributed temperature sensing (DTS) in-stream measurements for three cloud-free days in August 2007 over a 1260 m stretch of the Boiron de Merges River in southwest Switzerland were used to calibrate and validate a physically based one-dimensional stream temperature model. Stream temperature response to three distinct riparian conditions were then modeled: open, in-stream reeds, and forest cover. Simulation predicted a mean peak stream temperature increase of 0.7 °C if current vegetation was removed, an increase of 0.1 °C if dense reeds covered the entire stream reach, and a decrease of 1.2 °C if a mature riparian forest covered the entire reach. Understanding that full vegetation canopy cover is the optimal riparian management option for limiting stream temperature, in-stream reeds, which require no riparian set-aside and grow very quickly, appear to provide substantial thermal control, potentially useful for land-use management.

Pure FSH for ovulation induction in patients with polycystic ovary syndrome and resistant to clomiphene citrate therapy.

Twenty-nine infertile women with polycystic ovary disease which was resistant to therapy with clomiphene citrate underwent a combined treatment for follicle recruitment consisting of pure FSH during the first days of the cycle and HMG during the last days of the follicular phase. Sixty cycles were stimulated of which 83% were ovulatory. Eighteen pregnancies were achieved (36% of cycles, 62% of patients). The multiple pregnancy rate was 39%. Twelve cycles (20%) showed the ovarian hyperstimulation syndrome (OHS) although seven of these resulted in full term deliveries. There were no miscarriages among the patients studied.

[Cerebral metastasis of a cervix carcinoma]. / Zerebrale Metastase eines Zervixkarzinoms.

We present our first case of cerebral metastasis from cervical carcinoma in a living patient after primary treatment of the tumor. The metastasis was surgically removed, with a bad outcome. The lack of guidelines for the treatment of this complication, which is due to its extremely low frequency, is discussed.