Hormonal treatment as endometrial preparation for frozen-thawed embryo transfer (FET) is routinely carried out with oral, transdermal or combined estradiol supplementation; however, in some cases, there is no optimal endometrial development with this type of stimulation. In this case report, our patient failed to respond to conventional endometrial preparation techniques. For this reason, two unconventional techniques were combined to improve endometrial receptivity; endometrial injury, followed by rFSH administration. As a result of this combination, we achieved endometrium thickness, reaching 8.9 mm on day 15 of the cycle, carrying out the embryo transfer of two blastocysts on day-17 of the cycle, achieving clinical pregnancy and carrying it to completion with the birth of a baby.

To determine and compare metabolite content using magnetic resonance spectroscopy (MRS) of growing follicles in patients with polycystic ovary syndrome (PCOS) receiving recombinant follicle stimulating hormone (rFSH), clomiphene citrate (CC) or aromatase inhibitor (AI) for ovarian stimulation.
Thirty patients diagnosed with PCOS and infertility and scheduled for ovarian stimulation were divided by therapy, rFSH/CC/AI, into three equal groups. Five fertile cases were designated as the control group. When the follicle diameters reached 16-18 mm in each group, patients underwent MRS and the metabolite content of a dominant follicle was analyzed. N-acetylaspartate, lactate (Lac), creatine (Cr), and choline (Cho) metabolite levels in parts per million were measured in the spectra.
A ~three-fold decrease in dominant follicle Cho content was found in patients receiving CC compared to control subjects. Similarly, the dominant follicle Cho intensities of patients given rFSH and AI were noted to be significantly higher than those who received CC. Only dominant follicle Lac levels of the patients who received CC were found to be significantly higher than the other groups. Cr peak intensities of patients receiving CC were found to be approximately three times less than control subjects. Cr signal intensity was significantly higher in patients receiving rFSH or AI than in patients receiving CC. While two patients became pregnant in the CC group, three patients in the AI group and five patients in the rFSH group became pregnant. The main metabolites detected in patients who conceived in each group were Cho and Cr. In cases who could not conceive, while Lac and lipid signals increased, Cho and Cr signals decreased.
Unlike CC, ovarian stimulation with rFSH or AI does not alter dominant follicle metabolite content. The developmental capacity of a growing egg may be determined non-invasively with MRS.

The aim of the present study is to investigate embryo quality (score) after controlled ovarian stimulation for IVF using rFSH or hMG with the GnRH antagonist protocol.
Open, randomized, single center study. The patients were randomized to receive rFSH or hMG according to randomized cards inside a black envelope with the name of the respective treatment following a computer generated list (85 patients were allocated to rFSH group and 83 patients to hMG group). Inclusion criteria were patients with IVF indication and normal ovarian reserve. Embryo evaluation was performed on day three, after fertilization based on the Graduated Embryo Score (GES).
There were no relevant differences in demographic characteristics. There was no difference in pregnancy rates with 27 (31%) and 25 (30.1%) pregnancies for rFSH and hMG, respectively (p=0.87). The total embryo score was the same for both groups, but the best embryo score was significant higher for the rFSH group (77.33±34.0 x 65.07±33.2 p=0.03). The total number of embryos was statistical different, also in favor of the rFSH group (4.17±3.1 x 3.26±2.4 p=0.04).
The total embryo score was the same for both groups, but the best embryo score was significantly higher for the rFSH group. Moreover, rFSH was associated with an increased number of embryos.

While luteinizing hormone (LH) activity is believed to play a role in follicle maturation, human chorionic gonadotropin (hCG) might play an important role in implantation process. We aimed to investigate whether addition of human menopausal gonadotropin (hMG) in recombinant-follicle-stimulating hormone (r-FSH) started GnRH antagonist controlled ovarian hyperstimulation (COH) cycles might enhance implantation rate and improve in vitro fertilization (IVF) success. A total of 246 patients undergoing GnRH antagonist IVF cycles were analyzed. One hundred and twenty-three cycles (%50) were treated with only r-FSH and 123 cycles were treated with r-FSH plus hp-hMG combination. Total gonadotropin doses, total number of oocytes retrieved, metaphase 2 (MII) oocytes, top quality embryos, fertilization and implantation rates, clinical pregnancy rates (CPRs) and ovarian hyperstimulation syndrome (OHSS) rates were compared between the groups. Both groups were comparable in terms of demographic details and baseline characteristics. Peak estradiol and progesterone levels in hCG trigger day, number of retrieved oocytes and top quality embryo counts, fertilization rates were similar between the groups. In r-FSH + hp-hMG group, significantly higher implantation rates (35.3% vs 24.3%, p=.017), CPRs (51.2% vs 35.8%, p=.015) and lower OHSS rates (1.6% vs 7.4%, p = .03) were observed respectively compared to r-FSH only treated patients. In conclusion, addition of hp-hMG on the day of antagonist initiation might increase CPRs. A better endometrial receptivity associated with higher implantation rates might be achieved due to hCG component in hp-hMG.

Ovarian monitoring requires the determination of serum estradiol and progesterone levels. We investigated whole follicular steroidogenesis under rFSH in medically assisted procreation (MAP: 26 IVF, 24 ICSI) compared to 11 controls (IUI). Estrone, estradiol, Δ4-androstenedione, testosterone, progesterone and 17-hydroxyprogesterone were measured by immunoassay and mass spectrometry except for estrogens. At the start of a spontaneous or induced cycle, steroids levels fluctuated within normal ranges: estradiol (314-585 pmol/L), estrone (165-379 pmol/L) testosterone (1.3-1.6 nmol/L), Δ4-androstenedione (4.5-5.6 nmol/L), 17-hydroxyprogesterone (2.1-2.2 nmol/L) and progesterone (1.8-1.9 nmol/L). 17-hydroxyprogesterone, Δ 4-androstenedione and estradiol predominated. Then estradiol and oestrone levels rise, but less markedly for oestrone in IUI. In MAP, rFSH injections induce a sharp increase in estrogens associated with a rise in 17-hydroxyprogesterone and Δ4-androstenedione levels, disrupting oestrogen/androgen ratios. rFSH stimulation induces an ovarian hyperplasia and Δ4pathway which could become abnormal. Determining 17-hydroxyprogesterone and Δ4-androstenedione levels with LC-MS/MS may therefore be useful in managing recurrent MAP failures.

OBJECTIVE: To determine whether the addition of either urinary or recombinant LH in patients undergoing routine clinical care improved the outcome in terms of the number of oocytes recovered for insemination or the delivery rate per initiated cycle.
METHODS: Cohort analysis.
METHODS: Couples undergoing IVF/ICSI in 158 institutions in 15 countries in Latin America.
METHODS: In vitro fertilization clinics.
METHODS: We compared the outcome of three different protocols of COH, including rFSH only, rFSH plus rLH, and rFSH plus hMG.
METHODS: The number of mature oocytes recovered and inseminated; proportion of ETs at the blastocyst stage; clinical pregnancy, miscarriage, and delivery rates; proportion of cycles with embryo cryopreservation; and mean number of embryos cryopreserved.
RESULTS: After correcting for the age of the female partner, body mass index, number of embryos transferred, and stage of embryo development at transfer, we found that LH addition was not associated with an increase in the mean number of metaphase II oocytes inseminated or with an increase in the delivery rate or changes in the miscarriage rate.
CONCLUSIONS: Our study strongly suggests that in routine clinical practice, the type of controlled ovarian stimulation-FSH alone or in combination with LH-has little impact on the outcome of assisted reproductive technology; therefore a more friendly and accessible alternative should be favored.

OBJECTIVE: To examine the efficacy and safety of frozen-thawed embryo transfer (FTET) cycles with supernumerary embryos cryopreserved during a randomized clinical trial (PURSUE).
METHODS: Follow-up clinical study.
METHODS: In vitro fertilization (IVF) centers.
METHODS: Infertile women 35 to 42 years of age.
METHODS: In PURSUE, women were randomized to a single injection of 150 μg of corifollitropin alfa (n = 694) or daily 300 IU of recombinant follicle-stimulating hormone (recombinant FSH; n = 696) for the first 7 days of controlled ovarian stimulation (COS) in a gonadotropin-releasing hormone (GnRH) antagonist protocol.
METHODS: Cumulative vital pregnancy rate per-patient by treatment group, cumulative live-birth rate per-patient by treatment group, and occurrence of adverse events in (pregnant) women and their fetuses/infants and the incidence of congenital malformations in the infants.
RESULTS: Of the 1,390 treated women in PURSUE, 307 were enrolled in the FTET study. In PURSUE or a subsequent FTET cycle, the cumulative vital pregnancy rate (per patient) was 31.1% (95% confidence interval [CI], 27.7%; 34.7%) with corifollitropin alfa versus 33.0% (95% CI: 29.6%; 36.7%) with recombinant FSH; treatment difference, -1.8% (95% CI, -6.5%; 3.0%), and the cumulative live-birth rate (per patient) was 28.2% (95% CI, 24.9%; 31.8%) with corifollitropin alfa versus 29.5% (95% CI, 26.1%; 33.0%) with recombinant FSH; treatment difference, -1.2% (95% CI, -5.7%; 3.4%). There were no clinically relevant differences in safety outcomes collected from pregnant women or their infants after transfer of cryopreserved embryos obtained by treatment with corifollitropin alfa or recombinant FSH.
CONCLUSIONS: The cumulative vital pregnancy and live-birth rates (from fresh cycles and FTET) were similar in women treated with corifollitropin alfa and recombinant FSH. No new safety signals were detected in this follow-up FTET study.
BACKGROUND: NCT01146418.

UNASSIGNED: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.
Ciddi enjeksiyon hatası olan bir olgu sunuyoruz: Erkek faktörünün yol açtığı ikincil infertilitesi olan 25 yaşındaki bir kadın IVF/ICSI-ET programımıza alındı. Stimulasyon uzun protokol ile gerçekleştirildi ve over stimulasyonu, rFSH follitropin beta kullanılarak, menstrüel döngünün üçüncü günü başlatıldı. Günlük rFSH dozu şöyleydi: 900 IU-0 IU-0 IU-0 IU. Normal over yanıtı ve folikül büyümesi nedeniyle stimulasyona devam edildi, oosit kalitesinde bozulma ve OHSS semptomları yoktu. Blastokist transferini takiben sezaryenle doğum, kalıcı transvers duruş nedeniyle 37+5’inci gebelik haftasında önlenemez durumdaydı. Çeşitli hastaların uygun tedavisi için, tedavi uygulamasının doğru bir şekilde yapılmasını sağlayan, farklı stimulasyon protokollerine gerek duyulmaktadır. Enjeksiyon hataları durumunda, hormon düzeyleri ve folikül büyümesi süreci göz önüne alınarak, stimulasyon protokolünün sürdürülmesi bazı olgularda başarılabilir görünmektedir.

OBJECTIVE: To compare the impact of elevated P during the late follicular phase on the chance of pregnancy in low, normal, and high responders.
METHODS: Retrospective combined analysis from six clinical trials.
METHODS: IVF centers.
METHODS: Women up to 39 years of age with a regular menstrual cycle and an indication for ovarian stimulation before IVF/intracytoplasmic sperm injection.
METHODS: Ovarian stimulation with recombinant (r) FSH in a GnRH antagonist protocol.
METHODS: Ongoing pregnancy rates (OPRs) assessed with the use of univariate and multivariate analyses according to serum P levels ≤ 1.5 ng/mL versus >1.5 ng/mL on the day of hCG administration and compared among low (1-5 oocytes), normal (6-18 oocytes), and high (>18 oocytes) responders.
RESULTS: A total of 157/1,866 women (8.4%; 95% confidence interval [CI] 7.2%-9.8%) had elevated P. Incidence of elevated P increased from 4.5% in low responders to 19.0% in high responders. Overall, OPRs were significantly lower in women with elevated P. Per started cycle, the >1.5 to ≤ 1.5 ng/mL adjusted odds ratio was 0.55 (95% CI 0.37-0.81). OPRs were not impaired in high responders with P elevation and were significantly higher compared with normal responders with P elevation.
CONCLUSIONS: The incidence of elevated P increases with ovarian response, and elevated P at a threshold of 1.5 ng/mL is independently associated with a decreased chance of pregnancy in low to normal responders, but not in high responders, when using an rFSH/GnRH antagonist protocol.