Demographic distributions and clinical results of assisted reproduction techniques in Turkey in 2019: a descriptive survey.

Objective: The aim of this study was to describe characteristics and outcomes of assisted reproductive technology (ART) cycles performed in 2019 in Turkey. Material and Methods: One-hundred and sixty-five ART centers in Turkey were invited to submit data. The survey was sent to center directors via e-mail with anonymous links by Qualtrics™. The survey involved questions about their patient characteristics, clinical practices, and outcomes. Results: Forty-one (24.8%) centers responded to e-mails, and data gathered from 25 centers was included in the analyses. In 25 centers, 18,127 fresh or frozen transfers were carried out during the study period, of which 7796 (43.0%) were fresh and the rest were either frozen (45.2%) or embryo transfers (ET) with preimplantation genetic testing (PGT) (11.8%). The live birth rate per ET was as 30.6%, 40.1%, and 50.7% in fresh, frozen and PGT cycles, respectively. A single embryo was transferred in 65.3% of all transfers and singleton live births comprised 86.1% of all deliveries. For cycles with intrauterine insemination, 1407 were started in 2019, and 195 clinical pregnancies, 150 live births with 19 multiple pregnancies occurred. A total of 1513 ART cycles were initiated for foreign patients. Russia (29.6%), Germany (7.4%), Iraq (4.6%), Uzbekistan (3.1%), and Syria (1.4%) were the top five countries with most patients coming to Turkey for ART. Conclusion: The survey results are in parallel with the reports of international institutions and organizations. With repeated editions, the data collected with annual surveys can be used to inform ART practices in the coming years.

Comparison of ICSI and conventional IVF in non-male factor patients with less than four oocytes.

BACKGROUND: We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) to clarify if lower number of oocytes is a drawback for proceeding to C-IVF. MATERIALS AND METHODS: In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤ 3 cumulus-oocyte complexes available for fertilisation were analysed. Exclusion criteria were: woman age > 42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1, n = 77); ICSI non-male factor (Group 2, n = 65); ICSI male factor-ICSI/MF n = 49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. RESULTS: Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85.68%, 72.58%, 73.33% respectively, p = 0.004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20.42%, 28.49%, 23.33% respectively, p = 0.407) and live birth rates (26.8%, 30.6%, 31.1%, respectively, p = 0.643). CONCLUSION: In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient's previous history regardless of the ovarian reserve.

The experience of in vitro fertilization data collection in Turkey

Collecting and reporting data is a crucial aspect of in vitro fertilization (IVF) practice. During the following two decades after the first report of the European IVF-monitoring Consortium (EIM) on IVF data, the number of contributing countries increased gradually reaching nearly forty. For the first seven years of publication, between 2001 and 2007, Turkey did not provide IVF data to the European registry. Turkey first took part in the European registry in 2008 and thus also in the World registry. The addition of Turkish data to EIM was an important milestone, since Turkey appeared as the country with the sixth highest number of cycles, performing nearly eight percent of all European assisted reproductive technology (ART) cycles. Turkey continued contributing to the European registry for the following four years consecutively but after 2012 the input of Turkish IVF data stopped. Strikingly, between 2008-2012 Turkey became one of the main contributors to the registry with an ability to give a full report. So far, we do not have a complete European set of data and the number of cycles reported by European Society for Human Reproduction and Embryology (ESHRE) EIM can easily be said to be an underestimation of the actual number of cycles. IVF data from Turkey - a country having the 17th highest population in the World and appearing among the first six countries in Europe in terms of the number of ART cycles per year- will definitely contribute very much to ESHRE EIM database. It is now time to turn the tide and restart submitting Turkish data to European registry, but this time regularly and in a systematic method. Such an achievement will greatly contribute to the aim of EIM of achieving a complete data set.

Modified natural protocol seems superior to natural and artificial protocols for preparing the endometrium in frozen embryo transfer cycles.

BACKGROUND: Although several studies claim higher success rates in natural cycle (NC) and modified natural cycle (mNC) protocols, currently, there is no consensus on the most effective method of endometrium preparation prior to frozen embryo transfer (FET) cycles. We aimed to find out the best protocol by comparing three different protocols for preparing the endometrium in FET cycles. METHODS: This retrospective cohort study was conducted at a private in-vitro fertilization (IVF) center. Medical records of all patients enrolled in frozen embryo transfer cycles between November 2017 and February 2019 were reviewed. Group I (N.=94) included patients who underwent artificial endometrial preparation (AC), group II (N.=23) confined patients enrolled in mNC and group III (N.=12) included patients who had NC protocol. Main outcome parameters were clinical pregnancy rates, implantation rates and miscarriage rates. RESULTS: There was a tendency towards higher clinical pregnancy rate in mNC group. Clinical pregnancy rates of the three groups were 54.3%, 65.2% and 33.3% respectively (P=0.199). Implantation rate was significantly higher in group II (34%, 50% and 12% respectively, P=0.006). Miscarriage rates were similar for the three groups. CONCLUSIONS: Although not reaching a statistically significant level, there is a tendency towards higher implantation rate and pregnancy rate in mNC protocol compared to true NC and AC protocols.

IVF staff attitudes towards oocyte donation: a multi-centric study from Iran and Turkey.

The aim of this descriptive study was to evaluate the attitudes and knowledge of IVF staff towards oocyte donation (OD) programme. A total of 163 individuals (19% men and 81% women) were requested to fill out a two-part questionnaire. Part 1 of the questionnaire contained general demographic information: 62% of the participants were married; the majority of the subjects had university education; 21% of the participants had high school degrees. Part 2 contained 20 questions to reveal the knowledge and attitudes of the participants concerning OD: 16% completely objected to OD; 50% of the married couples and 68% of the single individuals disagreed with OD treatment for themselves, even if they remained childless. Most participants believed in informing the general public about OD in the mass media. In addition, nearly half of the participants were in favour of OD over adopting a child. Psychological counselling was strongly recommended by the majority of respondents for both donors and the recipients. The majority of participants in the study had a positive attitude towards OD treatment for infertile couples. In addition, counselling can play a major role in OD programme. Therefore, the health professionals should advance the OD programmes for informing the staff of infertility centres and infertile patients.

What is the best time to perform intracytoplasmic sperm injection/embryo transfer cycle after hysteroscopic surgery for an incomplete uterine septum?

OBJECTIVE: To determine whether there is an optimal time period to perform intracytoplasmic sperm injection (ICSI)/embryo transfer cycle after hysteroscopic resection of an incomplete uterine septum. DESIGN: A retrospective cohort study. SETTING: Private infertility clinic. PATIENT(S): A total of 282 women, who had undergone an ICSI/embryo transfer cycle after hysteroscopic resection of an incomplete uterine septum (from May 6, 2003 to January 1, 2006). INTERVENTION(S): One hundred thirty-three patients (group A) underwent an ICSI/embryo transfer cycle within 9 weeks after hysteroscopic resection of an incomplete uterine septum, 93 patients (group B) underwent an ICSI/embryo transfer cycle between 10 and 16 weeks after hysteroscopic resection of an incomplete uterine septum, and 56 patients (group C) underwent an ICSI/embryo transfer cycle more than 17 weeks after hysteroscopic resection of an incomplete uterine septum. MAIN OUTCOME MEASURE(S): Peak E(2) levels, total recombinant FSH dosage, MII oocytes retrieved, number of embryos transferred, number of grade 1 embryo transferred, pregnancy rate (PR; positive hCG), clinical PR (positive fetal cardiac activity), implantation rate, and first trimester miscarriage rate. RESULT(S): Pregnancy rates were 52.6%, 52.6%, and 46.4% for groups A, B, and C, respectively. Clinical PRs were 45.8%, 43.1%, and 41.1% for groups A, B, and C, respectively. Implantation rates were 21.1%, 17.6%, and 22.1% for groups A, B, and C, respectively. First trimester miscarriage rates were 6.4%, 7.9%, and 5.1% for groups A, B, and C, respectively. There were no significant differences in the etiology of infertility, age, length of infertility, previous spontaneous abortion rates, length of septum, peak serum E(2) concentration, total recombinant FSH dosage, total number of MII oocytes retrieved, number of embryos transferred, number of grade 1 embryos transferred, PRs, clinical PRs, implantation rates, and first trimester miscarriage rate between the three groups. CONCLUSION(S): Starting an ICSI/embryo transfer cycle just after the hysteroscopic procedure does not result in any impairment in implantation rate or PR compared to those started 10 or more weeks after the operation.

Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection.

OBJECTIVE: To investigate the effect of continuous administration of gonadotropin-releasing hormone agonist (GnRHa) during the luteal phase in an intracytoplasmic sperm injection program. STUDY DESIGN: One hundred eighty-one women underwent a down-regulation protocol of GnRHa administered from the 21st day of the preceding cycle. Patients were randomized at initiation of stimulation by a computer-generated list. Group 1 patients (n = 90) were continuously administered GnRHa for 12 days after embryo transfer, while in group 2 patients GnRHa was stopped on the day of human chorionic gonadotropin administration. RESULTS: Demographic parameters, infertility etiologies, number of gonadotropin ampules used, number of mature oocytes recovered, rates of testicular sperm usage, number of embryos transferred, and cycle and transfer cancellation rates were similar in both groups. Clinical pregnancy rates, implantation rates and live birth rates did not show a significant difference. CONCLUSION: Extending GnRHa treatment through the luteal phase appeared not to have a significant impact on pregnancy or implantation rates in intracytoplasmic sperm injection cycles.

Is hysteroscopic correction of an incomplete uterine septum justified prior to IVF?

This retrospective study examined the effect of hysteroscopic correction of an incomplete uterine septum on IVF outcome. Measurement of the Fm (fundal myometrial thickness) and Cm (cornual myometrial thickness) was performed by sonohysterography. Group 1 included patients diagnosed with incomplete septum (n = 119), fulfilling the two criteria of Fm >11 mm and Fm-Cm >5 mm, who underwent hysteroscopic incision of the incomplete septum. Group 2 consisted of 116 age-matched control patients with a normal uterine cavity who underwent IVF within the same time period. Main outcome measures were clinical pregnancy and spontaneous abortion rates. Patients in group 1 had a history of more spontaneous abortions than patients in group 2 (14.20 versus 6.03%, P = 0.04) as well as higher previous IVF failure (32.7 versus 20.6%, P = 0.04). After surgical correction of the septum in group 1, IVF pregnancy outcome was similar in both groups (clinical pregnancy and pregnancy loss of 47.80 versus 46.50% and 10.52 versus 20.3% respectively). A similar pregnancy outcome was found after the incision of the incomplete septum compared with a group with normal uterine cavity. Larger prospective and randomized controlled studies are needed to prove the positive effect of correction of an incomplete uterine septum on IVF outcome.

Human albumin does not prevent ovarian hyperstimulation syndrome in assisted reproductive technology program: a prospective randomized placebo-controlled double blind study.

We aimed to clarify the efficiency of IV human albumin in the prevention of ovarian hyperstimulation syndrome (OHSS). We found that human albumin at the described strength does not seem to either prevent or reduce the incidence of severe OHSS in high risk patients undergoing intracytoplasmic sperm injection (ICSI).

Clinical effects of ovulation induction with recombinant follicle-stimulating hormone supplemented with recombinant luteinizing hormone or low-dose recombinant human chorionic gonadotropin in the midfollicular phase in microdose cycles in poor responders.

OBJECTIVE: To assess the clinical effects of recombinant luteinizing hormone (LH) or low-dose recombinant human chorionic gonadotropin (hCG) supplementation administered in the midfollicular phase in microdose gonadotropin-releasing hormone analogue (GnRH-a) flare-up cycles. DESIGN: Prospective randomized study. SETTING: Private infertility clinic. PATIENT(S): A total of 170 women enrolled, with 145 women eligible for randomization. INTERVENTION(S): After randomization, 51 patients (group A) received only 600 IU of recombinant follicle-stimulating hormone (FSH) as the control group, 46 patients (group B) received 600 IU of recombinant FSH plus daily supplementation with 75 IU of recombinant luteinizing hormone, and 48 patients (group C) received 600 IU of recombinant FSH plus daily supplementation with 75 IU of recombinant hCG. MAIN OUTCOME MEASURE(S): Peak estradiol (E(2)) levels, days of stimulation with recombinant FSH, total recombinant FSH dosage, metaphase II oocytes retrieved, pregnancy rate (positive hCG levels), clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. RESULT(S): The pregnancy rates were 35.1%, 27.6% and 31.2% for groups A, B, and C, respectively. Clinical pregnancy rates were 27.1%, 27.5, and 21.8% for groups A, B, and C, respectively. There were no statistically significant differences in the age, peak serum E(2) concentration, total recombinant FSH dosage, days of stimulation with recombinant FSH, total number of metaphase II oocytes retrieved, number of embryos transferred, pregnancy rates, clinical pregnancy rates, or cancellation rates of stimulation and embryo transfer among the three groups. CONCLUSION(S): Additional exogenous LH activity in the form of either recombinant luteinizing hormone or low-dose recombinant hCG is unnecessary in microdose cycles to increase pregnancy rates.

Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients.

Severe type I plasminogen (PLG) deficiency has been causally linked to a rare chronic inflammatory disease of the mucous membranes that may be life threatening. Here we report clinical manifestations, PLG plasma levels, and molecular genetic status of the PLG gene of 50 patients. The most common clinical manifestations among these patients were ligneous conjunctivitis (80%) and ligneous gingivitis (34%), followed by less common manifestations such as ligneous vaginitis (8%), and involvement of the respiratory tract (16%), the ears (14%), or the gastrointestinal tract (2%). Four patients showed congenital occlusive hydrocephalus, 2 with Dandy-Walker malformation of cerebellum. Venous thrombosis was not observed. In all patients, plasma PLG levels were markedly reduced. In 38 patients, distinct mutations in the PLG gene were identified. The most common genetic alteration was a K19E mutation found in 34% of patients. Transient in vitro expression of PLG mutants R134K, delK212, R216H, P285T, P285A, T319_N320insN, and R776H in transfected COS-7 cells revealed significantly impaired secretion and increased degradation of PLG. These results demonstrate impaired secretion of mutant PLG proteins as a common molecular pathomechanism in type I PLG deficiency.

Serum anti-Müllerian hormone levels do not predict the efficiency of testicular sperm retrieval in men with non-obstructive azoospermia.

BACKGROUND: We aimed to determine whether serum concentrations of anti-Müllerian hormone (AMH) can be used as a tool for prediction of the efficacy of sperm retrieval. METHODS: This was a prospective cohort observational study. AMH levels were determined in 47 men presenting for infertility evaluation. Group 1 consisted of 24 infertile patients diagnosed with non-obstructive azoospermia. Group 1 was further divided into two subgroups. The patients with spermatozoa in their testicular samples constituted group 1a (n = 13), while the patients with absence of spermatozoa constituted group 1b (n = 11). Twenty-three normozoospermic fertile men constituted group 2. Serum AMH was measured before obtaining testicular specimens. RESULTS: Testicular spermatozoa were recovered in 13 out of the 24 patients (54%). Demographic characteristics of the three groups were similar. The difference between serum AMH levels among the three groups did not reach statistical significance. CONCLUSIONS: We speculated that although AMH is secreted predominantly into the seminiferous tubules, studying serum samples might be more advantageous than seminal plasma because the presence of seminal proteases could influence AMH levels in the latter. However, our results did not demonstrate differences in serum concentrations of AMH between the studied groups. Studies with extended patient populations focusing on seminal plasma concentrations of AMH are warranted.

Semen quality of smoking and non-smoking men in infertile couples in a Turkish population.

OBJECTIVE: This retrospective study was designed to reveal the effect of smoking on semen parameters in an infertile Turkish population. PATIENTS: Two hundred and ninety-six infertile males were triaged as nonsmokers, light smokers and heavy smokers. Semen volume; sperm density, motility and morphology were the main outcome measures. RESULTS: Rapidly progressing sperm ratio of the heavy smokers group was greater than that of the light smokers group (p<0.05). Morphologic evaluation results revealed better results for the nonsmokers than the heavy smokers in terms of tail anomalies and percent of coiled tails (p<0.05) CONCLUSIONS: In infertile Turkish men, heavy smoking was found to have detrimental effects on tail of the spermatozoon. Interestingly, heavy smokers have a higher percent of rapidly progressive sperm with respect to light smokers. Prospective studies will help determining the definite effect of smoking on semen quality.

Cornual heterotopic pregnancy: conservative treatment with transvaginal embryo reduction.

OBJECTIVE: The objective was to discuss a case of heterotopic cornual pregnancy managed with transvaginal embryo reduction. METHODS: A 22-year-old woman with heterotopic cornual pregnancy was treated with ultrasonographically guided transvaginal injection of potassium chloride into the thorax of ectopic fetus. RESULTS: Sixteen days after the procedure, the patient presented with pelvic pain and miscarriage ensued. Control examination 1 month and 3 months later revealed normal uterine cavity and partially resorbed ectopic material. CONCLUSION: This minimally invasive approach in a hemodynamically stable patient can be considered in the management of a first trimester heterotopic cornual pregnancy. However the patient must be informed for the risk of abortion related to the procedure. Nevertheless this approach can be a treatment option in cornual pregnancies without a simultaneous intrauterine gestation.

Hypermobility syndrome in 105 women with pure urinary stress incontinence and in 105 controls.

We compared the frequency of Hypermobility Syndrome (HS) in 105 patients with urinary stress incontinence (USI) with the frequency of HS in 105 healthy controls that matched for age and parity. A Beighton score (BS) of more than 3 was used to make the clinical diagnosis of HS. Thirty-six patients (34.28%) from the USI group and 28 patients (26.66%) from the control group were diagnosed as HS. The mean BS values were 6.44+/-0.35 and 5.21+/-0.29 respectively. The difference between the two groups was statistically significant ( P<0.05).

Results of TVT operations alone and combined with other vaginal surgical procedures.

We made a study of 61 women with genuine stress incontinence (GSI). They all had a tension-free vaginal tape (TVT) and 28 patients had concomitant vaginal surgery. The cure rates and complication rates for the two groups were similar.

Biofeedback and pelvic floor exercises for the rehabilitation of urinary stress incontinence.

We investigated the effectiveness of pelvic floor muscle (PFM) exercises or biofeedback for the treatment of urinary stress incontinence (USI). Fifty patients with USI were included in this randomized, controlled, prospective study. Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program. The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months. The third group of 10 patients did not have any exercises. The patients were evaluated via pad test, perineometry, digital palpation based PFM strength, incontinence frequency, and visual analog scale based social activity index prior to and 8 weeks after the treatment. The first two groups had significant improvement in USI with respect to the control group (p < 0.001). The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment (p < 0.001). PFM exercises are effective for the treatment of USI; the biofeedback method revealed better PFM strength results with respect to digital palpation.

Rapid decline in ovarian reserve after repeated ART cycles in a 22-year-old IVF patient.

OBJECTIVE: The objective was to discuss the rapid decline in ovarian reserve due to repeated assisted reproductive technologies (ART) in a 22-year-old patient. METHODS: This case report presents an infertile couple admitted to our IVF unit with the diagnosis of recurrent implantation failure and congenital uterine anomaly. Main outcome measures were the number of growing follicles and metaphase II oocytes retrieved. RESULTS: After recurrent implantation failure of three in vitro fertilization cycles, the couple underwent three consecutive intracytoplasmic sperm injection cycles in our center. With a high number of oocytes retrieved, first cycle resulted in implantation failure followed by an embryo transfer cancelled cycle. The third cycle was cancelled due to an unexpected poor response even with the highest gonadotrophin dose. CONCLUSION: Rapid decrease in ovarian reserve should be considered when offering repeated ART cycles even if the woman is very young and has a good ovarian reserve.