Required amount of rFSH, HP-hMG and HP-FSH to reach a live birth: a systematic review and meta-analysis

Abstract

STUDY QUESTION In women undergoing IVF or ICSI cycles, do recombinant gonadotrophins differ from urinary-derived highly purified human menopausal gonadotropin (HP-hMG) or highly purified follicle-stimulating hormone (HP-FSH) in the total amount of gonadotrophins required to reach a live birth? SUMMARY ANSWER The difference between recombinant and urinary-derived HP-hMG or HP-FSH in the required amount to reach a live birth in IVF/ICSI cycles appears small. WHAT IS KNOWN ALREADY At present, gynecologists can choose between recombinant FSH (rFSH), urinary-derived HP-hMG and HP-FSH. These products are equally effective and safe, but it is unknown how these gonadotrophins compare in terms of IU required to reach a live birth. STUDY DESIGN, SIZE AND DURATION We conducted a search in Medline, Embase and CINAHL up to July 2018. We included randomized controlled trials (RCTs) that compared rFSH with HP-hMG or HP-FSH for ovarian stimulation in couples scheduled for IVF or ICSI treatment. From each randomized trial, we extracted the outcome data and information on participants, methods, interventions and funding. PARTICIPANTS/MATERIALS, SETTING AND METHODS Women undergoing ovarian stimulation with rFSH, HP-hMG or HP-FSH were included. We extracted data for the mean amount of gonadotrophins with SD, clinical pregnancy rate, live birth rate and cumulative live birth rate per woman from the included RCTs. We summarized these outcomes by calculating the individual and pooled mean difference (MD) or relative risk (RR) with 95% CI. We used the Review Manager software to perform the meta-analyses. We applied a random effect model to pool the data. We estimated the total amount of gonadotrophins used per extra live birth by STATA 14.2 and R software. MAIN RESULTS AND THE ROLE OF CHANCE A total of 28 studies with 7553 women were included in this review, of which 24 studies provided information on the total amount of gonadotrophins per woman who started an IVF/ICSI cycle. The total amount of gonadotrophins varied significantly between studies. The MDs in total amount were −37 IU (seven studies; N = 3220; 95% CI, −115 to 41; I 2 = 68%) for rFSH versus HP-hMG and −31 IU (17 studies; N = 3629; 95% CI, −290 to 228; I 2 = 97%) for rFSH versus HP-FSH. For rFSH versus HP-hMG, the RR for clinical pregnancy, live birth and cumulative live birth were 0.90 (95% CI, 0.81–1.00), 0.88 (95% CI, 0.78–0.99) and 0.91 (95% CI, 0.80–1.04), respectively. For rFSH versus HP-FSH, the RR for clinical pregnancy and live birth were 1.03 (95% CI, 0.94–1.13) and 1.03 (95% CI, 0.90–1.18), respectively; the data on cumulative live birth rate were lacking. The estimated difference in mean gonadotrophin amount per extra live birth was 789 IU (95% CI, ...

Randomized controlled trial comparing embryonic quality in rFSH versus hMG in IVF protocol with GnRH Antagonist

“…Our findings are in accordance to previous clinical randomized trials that compared rFSH and hMG in GnRH antagonist cycles ( Bordewijk et al , 2019 ; Bosch et al , 2008 ). They observed a lower number of oocytes retrieved with a mean difference of 3.1 in favor of the hMG group, and a lower number of MII oocytes with a mean difference of 1.9.…”

“…Many studies have compared rFSH and hMG in IVF cycles regarding their effectiveness in ovarian stimulation. Since hMG has a different composition, concerning the presence of LH, it has been speculated that this would affect the outcomes in follicular recruitment, follicular growth, number and quality of embryos and pregnancy rates ( Bordewijk et al , 2019 ; Zeleznik & Kubik, 1986 ; Ziebe et al , 2007 ).…”

The Influence Of Intrauterine Pressure On Embryo Retention In A Catheter After Embryo Transfer

“…21 In ET recipients, in addition to spontaneous contractions, the uterus is exposed to strong contractile stimuli arising from the transcervical passage of the transfer catheter and, in some cases, from using a tenaculum. 5,6 To achieve maximal relaxation of the uterus during ET, it is advised to perform ET gently, without excessive stimulation of the cervix. Other methods to inhibit excessive uterine contractions include lowering patient stress and using a myorelaxant, acupuncture, or an oxytocin antagonist.…”

“…Embryo transfer (ET) has been recognized as a vital step that influences pregnancy rates in patients undergoing in vitro fertilization (IVF). 1,2 To date, however, other stages of IVF have received more attention than ET, such as nutrition supplementation, 3,4 ovarian stimulation, 5,6 embryo incubation conditions, 7,8 endometrial scratching, 9,10 and luteal phase support. 11,12 Undoubtedly, the safe placement of embryos in the uterine cavity is essential to obtaining an optimal pregnancy rate, but there is no guarantee that embryos will remain in the uterine cavity after the procedure.…”

Human Recombinant FSH and Its Biosimilars: Clinical Efficacy, Safety, and Cost-Effectiveness in Controlled Ovarian Stimulation for In Vitro Fertilization

“…Preclinical data from animal models showed that the currently available r-hFSH medications have no teratogenic, mutagenic or clastogenic effects, an evidence that was further supported by a series of trials and meta-analysis regarding the safety and effectiveness of r-hFSH for women undergoing IVF [ 16 , 27 , 28 , 29 ], including poor responder patients of advanced age and women with polycystic ovary syndrome (PCOS) [ 30 ]. Pharmacokinetic studies showed that r-hFSH is no more detectable in the woman’s blood by the time of embryo implantation, and no detrimental effects on the fetus after accidental exposure to r-hFSH in early pregnancy have been reported; moreover, r-hFSH is not believed to increase the risk of abortion or affect birthweight [ 31 ].…”