Effects of gonadotropin administration on clinical outcomes in clomiphene citrate‐based minimal stimulation cycle IVF

Karakida, Shinya; Ezoe, Kenji; Fukuda, Junichiro; Yabuuchi, Akiko; Kobayashi, Tamotsu; Kato, Keiichi

doi:10.1002/rmb2.12310

Cited by 14 publications

(7 citation statements)

References 27 publications

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“…Karakida et al (21) measured the usefulness of adding gonadotropins in modi ed natural cycles, comparing it with the only addition of oral drugs (in this case, clomiphene citrate). After studying both groups, they discovered that although the number of oocytes per cycle obtained was greater for cycles with gonadotropins therapy, the cumulative LBR were comparable.…”

Section: Discussionmentioning

confidence: 99%

Returning to the Simplest Way: Clinical Results of Patients Undergoing Ivf in Natural Vs Modified Natural Cycles

Lopez¹,

Calzada²,

Cabada³

et al. 2022

Preprint

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Background In recent years, natural cycle IVF has been undergoing a revival, gaining recognition as a safer, cheaper, and more comfortable option for patients. we define natural cicle IVF as the treatment in which oocytes are obtained from a spontaneous ovulatory cycle. When oral drugs are used (usually clomiphene citrate or letrozole), the process is referred to as modified natural cycle IVF. The aim of this study is to clarify whether the introduction of oral medication is beneficial for patients. Methods We retrospectively analysed all natural or modified IVF treatments that took place in our clinic during the studied period (January 2016 - December 2020). Descriptive variables were analysed with a t-test, and a chi-square test was performed on result variables. Results We found significant differences in the number of oocytes obtained after oocyte retrieval was (1.03 vs 1.63, p<0.001), number of mature oocytes (0.9 vs 1.3, p < 0.01), fertilization rate (0.7 vs 1.1, p < 0.01), and number of embryos available for transfer (0.5 vs 0.7, p < 0.01).However, we did not found signficant differences in terms of pregnancy rate (26,3% vs 19,6%, p=0.251) or live birth rate (16.3% vs 14,3%, p=0.7806) Conclusions although the numbers of oocytes and embryos available were higher in the group that used oral medication (which is similar to that obtained in previous studies), we did not find any differences in success rates in terms of pregnancy or live birth rate. Adding oral medication to natural cycle IVF, although reducing cancellation rates, does not seem to have an impact on the clinical results of the cycle. More studies are necessary, but we could reconsider the need to add oral medication since they suppose a higher cost for the patient.

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Section: Discussionmentioning

confidence: 99%

Returning to the Simplest Way: Clinical Results of Patients Undergoing Ivf in Natural Vs Modified Natural Cycles

Lopez¹,

Calzada²,

Cabada³

et al. 2022

Preprint

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“…In the present study, for the oocyte retrievals, the ovarian stimulation used was only clomiphene citrate (CC) based minimal stimulation. The detailed protocol for minimal stimulation with CC has been previously reported [ 22 – 24 ]. Briefly, CC (50–100 mg/day; Fuji Pharma Co., Ltd., Tokyo, Japan) was orally administered from the 3rd day of the retrieval cycle to the day before induction of final oocyte maturation.…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, propensity score matching was performed using JMP software (SAS, Cary, NC, USA) to reduce the bias in patient characteristics, as previously reported [ 22 ]. All statistical analyses were performed using JMP software.…”

Section: Methodsmentioning

confidence: 99%

Letrozole-induced endometrial preparation improved the pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle: a retrospective cohort study

Ezoe¹,

Fukuda²,

Takeshima³

et al. 2022

BMC Pregnancy Childbirth

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Background Letrozole treatment is considered an effective option in endometrial preparation for frozen embryo transfers in patients with ovulation disorders or irregular menstruation; however, the effectiveness of letrozole-induced endometrial preparation remains unclear in ovulatory patients. Furthermore, there is no comparative study reporting on pregnancy complications and congenital anomalies after frozen embryo transfers comparing natural and letrozole-assisted cycles. This study examined whether letrozole-induced endometrial preparation affected pregnancy outcomes, perinatal outcomes, and congenital anomalies after single vitrified-warmed blastocyst transfers (SVBTs) in ovulatory patients, as compared with the natural cycle. Methods This historic cohort study included only patients with unexplained infertility. Overall, 14,611 patients who underwent SVBTs between July 2015 and June 2020, comprising both natural and letrozole-assisted cycles, were included. Multiple covariates that impact outcomes were used for propensity score matching; 1,911 patients in the letrozole group were matched to 12,700 patients in the natural group, and the clinical records of 1,910 patients in each group were retrospectively analysed. Cycle characteristics, pregnancy outcomes (clinical pregnancy, ongoing pregnancy, and live birth), and incidence of pregnancy complications and congenital anomalies were statistically compared between the two groups. Results Multivariate logistic regression analysis showed that letrozole administration during SVBT cycles significantly improved the live birth rate (P = 0.0355). Gestational age, birth length, birth weight, and infant sex, as well as the incidence of pregnancy complications and birth defects, were statistically comparable between the two groups. Furthermore, multivariate logistic regression analysis revealed that the perinatal outcomes were not affected by letrozole-induced endometrial preparation. Conclusions Letrozole-induced endometrial preparation improved the live birth rate compared with the natural cycle, without adverse effects on perinatal outcomes and congenital anomalies after SVBTs. Therefore, letrozole-induced endometrial preparation might be a safe and more effective strategy, especially for patients with insufficient luteal function.

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“…The detailed protocol for minimal stimulation with CC has been previously reported ( Kato et al , 2018 ; Karakida et al , 2020 ; Nishihara et al , 2020 ). In brief, CC (50–100 mg/day; Fuji Pharma Co., Ltd., Tokyo, Japan) was administered orally (with an extended regimen) from the third day of the retrieval cycle to the day before induction of final oocyte maturation.…”

Section: Methodsmentioning

confidence: 99%

Maternal and obstetric outcomes are influenced by developmental stage and cryopreservation of transferred embryos after clomiphene citrate-based minimal stimulation IVF

Onogi¹,

Ezoe²,

Kawasaki³

et al. 2022

Human Reproduction Open

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STUDY QUESTION Is the embryo transfer method associated with maternal and perinatal outcomes after minimal stimulation IVF using clomiphene citrate (CC)? SUMMARY ANSWER The incidence of pregnancy complications and adverse perinatal outcomes was influenced by the developmental stage (cleavage versus blastocyst stages) and cryopreservation (fresh versus vitrified) of the transferred embryos. WHAT IS KNOWN ALREADY Pregnancies resulting from IVF are associated with higher risks of adverse perinatal outcomes compared to natural conceptions; therefore, the next focus in reproductive medicine should be to assess whether these increased risks are attributable to IVF. Pregnancy complications and perinatal outcomes should be considered in addition to pregnancy outcomes when selecting the embryo transfer method, however studies that describe the influence of transfer methods on perinatal and maternal outcomes are limited. STUDY DESIGN, SIZE, DURATION This study retrospectively analysed a large single-centre cohort. The clinical records of 36,827 women who underwent oocyte retrieval (during a CC-based minimal stimulation cycle) followed by their first embryo transfer at the fertility treatment centre between January 2008 and December 2017 were retrospectively analysed. The patients underwent a single fresh cleavage-stage embryo transfer (SFCT), single vitrified-warmed cleavage-stage embryo transfer (SVCT), or single vitrified-warmed blastocyst transfer (SVBT). This study only included one cycle per patients. PARTICIPANTS/MATERIALS, SETTING, METHODS Oocyte retrieval was performed following CC-based minimal ovarian stimulation. The embryos were transferred 2–3 days after retrieval or vitrified at the cleavage or blastocyst stage. The vitrified embryos were then warmed and transferred within the natural cycles. Pregnancy complications and perinatal outcomes were stratified according to the transfer methods used. Multivariate logistic regression analysis was performed to evaluate the effect of embryo transfer methods on the prevalence of pregnancy complications and congenital anomalies. MAIN RESULTS AND THE ROLE OF CHANCE The rates of clinical pregnancy and delivery were significantly different among the groups. We analysed pregnancy complications in 7,502 singleton births (SFCT, 3,395 cycles; SVCT, 586 cycles; and SVBT, 3,521 cycles). Multivariate logistic regression analysis revealed that the adjusted odds ratio (AOR) for hypertensive disorders in pregnancy was significantly lower in the SVBT group than in the SFCT group [AOR, 0.72; 95% CI, 0.56–0.92]. The AOR for low-lying placenta was lower in the SVBT group than in the SFCT group (AOR, 0.34; 95% CI, 0.19–0.60). The AOR for placenta previa was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.21; 95% CI, 0.07–0.58 versus AOR, 0.53; 95% CI, 0.38–0.75, respectively). A total of 7,460 follow-up data on neonatal outcomes was analysed. The AOR for preterm delivery was lower in the SVBT group than in the SFCT group (AOR, 0.78; 95% CI, 0.64–0.94). The AOR for low birthweight was significantly lower after SVCT and SVBT than after SFCT (AOR, 0.68; 95% CI, 0.46–0.98 versus AOR, 0.57; 95% CI, 0.48–0.66, respectively). The AOR for SGA was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.68; 95% CI, 0.46–0.98 versus AOR, 0.44; 95% CI, 0.36–0.55, respectively). The AOR for LGA babies was higher in the SVBT group than in the SFCT group (AOR, 1.88; 95% CI, 1.62–2.18). The incidence of each congenital anomaly was similar among the groups. LIMITATIONS, REASONS FOR CAUTION The study data were collected through self-reported parental questionnaires on maternal and neonatal outcomes. Our findings were not compared with the incidence of pregnancy complications and congenital anomalies in natural pregnancies. Furthermore, this study was retrospective in nature; therefore, further studies are required to ascertain the generalisability of these findings to other clinics with different protocols and/or different patient demographics. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrated reassuring outcomes for SVBT (in terms of a lower incidence of pregnancy complications) compared to SFCT. Our findings provide valuable knowledge that will help improve perinatal and maternal outcomes in CC-based stimulation and inform couples of the possible benefits and risks of each type of embryo transfer method. STUDY FUNDING/COMPETING INTEREST(S) This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

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Effects of gonadotropin administration on clinical outcomes in clomiphene citrate‐based minimal stimulation cycle IVF

Cited by 14 publications

References 27 publications

Returning to the Simplest Way: Clinical Results of Patients Undergoing Ivf in Natural Vs Modified Natural Cycles

Returning to the Simplest Way: Clinical Results of Patients Undergoing Ivf in Natural Vs Modified Natural Cycles

Letrozole-induced endometrial preparation improved the pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle: a retrospective cohort study

Maternal and obstetric outcomes are influenced by developmental stage and cryopreservation of transferred embryos after clomiphene citrate-based minimal stimulation IVF

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