Mild versus conventional ovarian stimulation for IVF in poor, normal and hyper-responders: a systematic review and meta-analysis.

Abstract:

BACKGROUND:Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance. OBJECTIVE AND RATIONALE:To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF. SEARCH METHODS:Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology. OUTCOMES:A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost. WIDER IMPLICATIONS:This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with 'freeze-all' strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF.

journal_name

Hum Reprod Update

authors

Datta AK,Maheshwari A,Felix N,Campbell S,Nargund G

doi

10.1093/humupd/dmaa035

subject

Has Abstract

pub_date

2020-11-04 00:00:00

eissn

1355-4786

issn

1460-2369

pii

5955862

pub_type

杂志文章
  • Smoking and reproduction: gene damage to human gametes and embryos.

    abstract::Assisted conception is a useful methodology for detecting disturbances in clinical outcome, meiotic maturation, and genetic integrity of human gametes. Germinal cells are vulnerable to genetic damage from smoking, but can repair damage during meiosis. In ejaculated spermatozoa, repair capacity declines drastically. Sm...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/6.2.122

    authors: Zenzes MT

    更新日期:2000-03-01 00:00:00

  • Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis.

    abstract:BACKGROUND:The reproductive impact of adenomyosis and endometriosis is widely researched but the extent of these impacts remains elusive. It has been demonstrated that endometriosis, in particular, is known to result in subfertility but endometriosis and adenomyosis are increasingly linked to late pregnancy complicatio...

    journal_title:Human reproduction update

    pub_type: 杂志文章,meta分析

    doi:10.1093/humupd/dmz012

    authors: Horton J,Sterrenburg M,Lane S,Maheshwari A,Li TC,Cheong Y

    更新日期:2019-09-11 00:00:00

  • Novel reproductive technologies to prevent mitochondrial disease.

    abstract:BACKGROUND:The use of nuclear transfer (NT) has been proposed as a novel reproductive treatment to overcome the transmission of maternally-inherited mitochondrial DNA (mtDNA) mutations. Pathogenic mutations in mtDNA can cause a wide-spectrum of life-limiting disorders, collectively known as mtDNA disease, for which the...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmx018

    authors: Craven L,Tang MX,Gorman GS,De Sutter P,Heindryckx B

    更新日期:2017-09-01 00:00:00

  • The estrogen-macrophage interplay in the homeostasis of the female reproductive tract.

    abstract:BACKGROUND:Estrogens are known to orchestrate reproductive events and to regulate the immune system during infections and following tissue damage. Recent findings suggest that, in the absence of any danger signal, estrogens trigger the physiological expansion and functional specialization of macrophages, which are immu...

    journal_title:Human reproduction update

    pub_type: 杂志文章

    doi:10.1093/humupd/dmy026

    authors: Pepe G,Locati M,Della Torre S,Mornata F,Cignarella A,Maggi A,Vegeto E

    更新日期:2018-11-01 00:00:00

  • Women's emotional adjustment to IVF: a systematic review of 25 years of research.

    abstract::This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF t...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dml040

    authors: Verhaak CM,Smeenk JM,Evers AW,Kremer JA,Kraaimaat FW,Braat DD

    更新日期:2007-01-01 00:00:00

  • Access to and sustainability of abortion services: a systematic review and meta-analysis for the National Institute of Health and Care Excellence-new clinical guidelines for England.

    abstract:BACKGROUND:Induced abortion is a common procedure. However, there is marked variation in accessibility of services across England. Accessing abortion services may be difficult, particularly for women who live in remote areas, are in the second trimester of pregnancy, have complex pre-existing conditions or have difficu...

    journal_title:Human reproduction update

    pub_type: 杂志文章

    doi:10.1093/humupd/dmaa026

    authors: O'Shea LE,Hawkins JE,Lord J,Schmidt-Hansen M,Hasler E,Cameron S,Cameron IT

    更新日期:2020-11-01 00:00:00

  • IUI for unexplained infertility-a network meta-analysis.

    abstract:BACKGROUND:IUI for unexplained infertility can be performed in a natural cycle or in combination with ovarian stimulation. A disadvantage of ovarian stimulation is an increased risk of multiple pregnancies with its inherent maternal and neonatal complication risks. Stimulation agents for ovarian stimulation are clomiph...

    journal_title:Human reproduction update

    pub_type: 杂志文章,meta分析

    doi:10.1093/humupd/dmz035

    authors: Danhof NA,Wang R,van Wely M,van der Veen F,Mol BWJ,Mochtar MH

    更新日期:2020-01-01 00:00:00

  • Characterization of the ovarian transcriptome through the use of differential analysis of gene expression methodologies.

    abstract::Prior to the development of high-throughput methods for the analysis of differential gene expression, genes required for proper ovarian function were identified on a case-by-case basis. Recently, however, several techniques have been developed that enable investigators to study large-scale changes in gene expression u...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmh017

    authors: Hennebold JD

    更新日期:2004-05-01 00:00:00

  • Leiomyomata: heritability and cytogenetic studies.

    abstract::Leiomyomata represent the most common gynaecological tumour in women of reproductive age, and are the primary indication for hysterectomy in the USA. Cytogenetic and genetic studies have, in recent years, advanced our understanding of the aetiology of these tumours. Cytogenetic aberrations involving chromosomes 6, 7, ...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/7.1.8

    authors: Ligon AH,Morton CC

    更新日期:2001-01-01 00:00:00

  • The impact of periconceptional maternal lifestyle on clinical features and biomarkers of placental development and function: a systematic review.

    abstract:BACKGROUND:Worldwide, placenta-related complications contribute to adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction and preterm birth, with implications for the future health of mothers and offspring. The placenta develops in the periconception period and forms the interface between mother an...

    journal_title:Human reproduction update

    pub_type: 杂志文章

    doi:10.1093/humupd/dmy037

    authors: Reijnders IF,Mulders AGMGJ,van der Windt M,Steegers EAP,Steegers-Theunissen RPM

    更新日期:2019-01-01 00:00:00

  • Homocysteine--a pathophysiological cornerstone in obstetrical and gynaecological disorders?

    abstract::Homocysteine, a product of the methionine cycle, is known to play an important role in cardiovascular diseases, neurological disorders and embryology, and in very important, fast growing fields concerning obstetrics and gynaecology. Therefore, we attempted an actual overview on possible obstetrical and gynaecological ...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/5.1.64

    authors: Obwegeser R,Hohlagschwandtner M,Sinzinger H

    更新日期:1999-01-01 00:00:00

  • Balancing ovulation and anovulation: integration of the reproductive and energy balance axes by neuropeptides.

    abstract:BACKGROUND:Because of the substantial energy demands of reproduction, the brain must temper the fertility of individuals to match nutritional availability. Under-nutrition is associated with infertility in humans and animals. The brain uses adipose- and gut-derived hormones, such as leptin, insulin and ghrelin, to modu...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dms004

    authors: Evans JJ,Anderson GM

    更新日期:2012-05-01 00:00:00

  • Visually scoring hirsutism.

    abstract:BACKGROUND:Hirsutism is the presence of excess body or facial terminal (coarse) hair growth in females in a male-like pattern, affects 5-15% of women, and is an important sign of underlying androgen excess. Different methods are available for the assessment of hair growth in women. METHODS:We conducted a literature se...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmp024

    authors: Yildiz BO,Bolour S,Woods K,Moore A,Azziz R

    更新日期:2010-01-01 00:00:00

  • In vitro bioassays for androgens and their diagnostic applications.

    abstract::Androgen levels are measured in today's clinical practice almost exclusively by immunoassays. The androgen that is most frequently determined is testosterone (T), but sometimes also the levels of other testicular, ovarian and adrenal androgens such as 5alpha-dihydrotestosterone, androstenedione, dehydroepiandrosterone...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmm038

    authors: Roy P,Alevizaki M,Huhtaniemi I

    更新日期:2008-01-01 00:00:00

  • The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis.

    abstract:UNLABELLED:BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many ye...

    journal_title:Human reproduction update

    pub_type: 杂志文章,meta分析,评审

    doi:10.1093/humupd/dmt038

    authors: Zimmerman Y,Eijkemans MJ,Coelingh Bennink HJ,Blankenstein MA,Fauser BC

    更新日期:2014-01-01 00:00:00

  • Calcium signalling in human spermatozoa: a specialized 'toolkit' of channels, transporters and stores.

    abstract::Ca(2+) is a ubiquitous intracellular messenger which encodes information by temporal and spatial patterns of concentration. In spermatozoa, several key functions, including acrosome reaction and motility, are regulated by cytoplasmic Ca(2+) concentration. Despite the very small size and apparent structural simplicity ...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmi050

    authors: Jimenez-Gonzalez C,Michelangeli F,Harper CV,Barratt CL,Publicover SJ

    更新日期:2006-05-01 00:00:00

  • Contraception and HIV infection in women.

    abstract:BACKGROUND:More than 15 million women, many of reproductive age, were infected with human immunodeficiency virus (HIV) at the end of 2007. As the HIV epidemic evolves, heterosexual intercourse is increasingly risky: the risk of infection in exposed young women is 4- to 7-fold higher than in young men and nearly half a ...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmn049

    authors: Heikinheimo O,Lähteenmäki P

    更新日期:2009-03-01 00:00:00

  • Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century.

    abstract:BACKGROUND:Infertility is estimated to affect as many as 186 million people worldwide. Although male infertility contributes to more than half of all cases of global childlessness, infertility remains a woman's social burden. Unfortunately, areas of the world with the highest rates of infertility are often those with p...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmv016

    authors: Inhorn MC,Patrizio P

    更新日期:2015-07-01 00:00:00

  • Low-dose aspirin for in vitro fertilization: a systematic review and meta-analysis.

    abstract::Despite recent advances in ovarian stimulation regimens and laboratory techniques, the pregnancy rate of assisted reproduction remains relatively low. New methods that would potentially improve implantation rates are needed. One proposed strategy involves enhancement of blood flow at the implantation site with the use...

    journal_title:Human reproduction update

    pub_type: 杂志文章,meta分析,评审

    doi:10.1093/humupd/dmm005

    authors: Gelbaya TA,Kyrgiou M,Li TC,Stern C,Nardo LG

    更新日期:2007-07-01 00:00:00

  • Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis.

    abstract:BACKGROUND:Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE...

    journal_title:Human reproduction update

    pub_type: 杂志文章,meta分析

    doi:10.1093/humupd/dmz048

    authors: van Dijk MM,Kolte AM,Limpens J,Kirk E,Quenby S,van Wely M,Goddijn M

    更新日期:2020-04-15 00:00:00

  • Regulation of male fertility by CFTR and implications in male infertility.

    abstract:BACKGROUND:The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl(-) and HCO(3)(-) conducting channel, mutations of which are known to be associated with male infertility. However, the underlying mechanisms remain elusive. METHODS:Literature databases were searched for papers on the topi...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dms027

    authors: Chen H,Ruan YC,Xu WM,Chen J,Chan HC

    更新日期:2012-11-01 00:00:00

  • Changes in basement membrane thickness in the human endometrium during the luteal phase of the menstrual cycle.

    abstract::We have examined aspects of the fine structure of the basal laminae associated with the luminal and glandular epithelium and small blood vessels in the human endometrium. Four short studies are presented and reviewed. Study 1 examined biopsies from 20 fertile women taken on days after the luteinizing hormone surge (LH...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/4.5.486

    authors: Dockery P,Khalid J,Sarani SA,Bulut HE,Warren MA,Li TC,Cooke ID

    更新日期:1998-09-01 00:00:00

  • Secondary recurrent miscarriage and H-Y immunity.

    abstract:BACKGROUND:Approximately half recurrent miscarriage (RM) cases remain unexplained after standard investigations. Secondary RM (SRM) is, in contrast to primary RM, preceded by a birth, which increases the transfer of fetal cells into the maternal circulation. Mothers of boys are often immunized against male-specific min...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmr005

    authors: Nielsen HS

    更新日期:2011-07-01 00:00:00

  • Cryopreservation of testicular tissue in young cancer patients.

    abstract::Cryopreservation of testicular tissue might benefit prepubertal boys who must undergo chemotherapy or radiotherapy. Cryopreservation of testicular tissue and testicular cells for intracytoplasmic sperm injection (ICSI) is feasible and widely applied. Testicular tissue from prepubertal boys can also be frozen, by apply...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/7.4.378

    authors: Hovatta O

    更新日期:2001-07-01 00:00:00

  • Protamines and male infertility.

    abstract::Protamines are the major nuclear sperm proteins. The human sperm nucleus contains two types of protamine: protamine 1 (P1) encoded by a single-copy gene and the family of protamine 2 (P2) proteins (P2, P3 and P4), all also encoded by a single gene that is transcribed and translated into a precursor protein. The protam...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dml009

    authors: Oliva R

    更新日期:2006-07-01 00:00:00

  • Hormonal contraception: what is new?

    abstract::Hormonal contraception has become more effective and more widely used, while the world population has grown from 3000 million in 1960 to 6000 million in 2000. There is a need for improved contraception, because legal abortion is used in a high proportion of pregnancies and illegal abortion continues to be common in so...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/8.4.359

    authors:

    更新日期:2002-07-01 00:00:00

  • Intrauterine devices and intrauterine systems.

    abstract::From a public health viewpoint, the intrauterine device (IUD) is the most widely used contraceptive method in the world. Prevalence rates range among countries from 2 to 80% of contraceptive users. During 5 years of IUD use, pregnancy occurs in less than 2 per 100 insertions. Bleeding and pain are the most common reas...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmn003

    authors: ESHRE Capri Workshop Group.

    更新日期:2008-05-01 00:00:00

  • Control and impairment of immune privilege in the testis and in semen.

    abstract::It has long been known that the testis is an immunologically privileged site in the body, and that human seminal plasma possesses a generalized immunosuppressive activity. Multiple factors participate in the establishment of immunotolerance in the testis: the blood-tubular barrier; the local production of immunosuppre...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/7.5.444

    authors: Filippini A,Riccioli A,Padula F,Lauretti P,D'Alessio A,De Cesaris P,Gandini L,Lenzi A,Ziparo E

    更新日期:2001-09-01 00:00:00

  • Dynamics and ethics of comprehensive preimplantation genetic testing: a review of the challenges.

    abstract:BACKGROUND:Genetic testing of preimplantation embryos has been used for preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Microarray technology is being introduced in both these contexts, and whole genome sequencing of blastomeres is also expeted to become possible soon. The amount of...

    journal_title:Human reproduction update

    pub_type: 杂志文章,评审

    doi:10.1093/humupd/dmt009

    authors: Hens K,Dondorp W,Handyside AH,Harper J,Newson AJ,Pennings G,Rehmann-Sutter C,de Wert G

    更新日期:2013-07-01 00:00:00

  • Can dopamine agonists reduce the incidence and severity of OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis.

    abstract:BACKGROUND:Recently, dopamine agonists were proposed as a prophylactic treatment for ovarian hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment cycles. METHODS:We conducted a systematic review and meta-analysis of randomized trials comparing the prophylactic effect of the dopamine agonist, ca...

    journal_title:Human reproduction update

    pub_type: 杂志文章,meta分析,评审

    doi:10.1093/humupd/dmq006

    authors: Youssef MA,van Wely M,Hassan MA,Al-Inany HG,Mochtar M,Khattab S,van der Veen F

    更新日期:2010-09-01 00:00:00