Management of Infertility

Project Summary Title and Description

Title
Management of Infertility
Description
Objective. Previous studies have demonstrated varying success for treatment of infertility. Much of this literature however does not focus on treatment of women with specific diagnoses. This systematic review evaluated the comparative effectiveness and safety of fertility treatment strategies for (a) women of reproductive age (18-44) who are infertile due to polycystic ovary syndrome (PCOS), endometriosis, unknown reasons, or tubal or peritoneal factors or (b) couples with male factor infertility; and evaluated short- and long-term health outcomes of gamete donors in infertility. Data sources. We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for English-language studies published from January 1, 2007, to October 3, 2018, that reported live birth rates, pregnancy and neonatal outcomes, time to pregnancy, and short-term and long-term adverse outcomes for mothers and children born after infertility treatment. For male and female donors, we searched for studies reporting short- and long-term adverse effects and quality-of-life outcomes. Review methods. Two investigators screened each abstract and full-text article for inclusion; abstracted data; and performed quality ratings, applicability ratings, and evidence grading. Where appropriate, random-effects models were used to compute summary estimates of effects.
Attribution
N/A
Authors of Report
N/A
Methodology description
We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for English-language studies published from January 1, 2007, to October 3, 2018. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. See the review protocol (https://effectivehealthcare.ahrq.gov/topics/infertility/research-protocol) for full details.
PROSPERO
CRD42016025750
DOI
10.26300/8nk3-sn76
Notes
This project was entered retrospectively. All Data Abstraction is available in the attached file: Infertility_Data_Upload.docx
Funding Source
Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. KQ 1: What are the comparative safety and effectiveness of available treatment strategies for women with polycystic ovary syndrome (PCOS) who are infertile and who wish to become pregnant? o a. Does the optimal treatment strategy vary by patient characteristics such as age, ovarian reserve, race, body mass index (BMI), presence of other potential causes of female infertility, or presence of male factor infertility?
2. KQ 2: What are the comparative safety and effectiveness of available treatment strategies for women with endometriosis who are infertile and who wish to become pregnant? o a. Does the optimal treatment strategy vary by patient characteristics such as age, ovarian reserve, race, BMI, stage of endometriosis, presence of other potential causes of female infertility, or presence of male factor infertility?
3. KQ 3: What are the comparative safety and effectiveness of available treatment strategies for women who are infertile for unknown reasons and who wish to become pregnant? o a. Does the optimal treatment strategy vary by patient characteristics such as age, ovarian reserve, race, BMI, presence of other potential causes of female infertility, or presence of male factor infertility?
4. KQ 4: What are the comparative safety and effectiveness of available treatment strategies for women with tubal or peritoneal factors (e.g., pelvic adhesions) who are infertile and who wish to become pregnant? o a. Does the optimal treatment strategy vary by patient characteristics such as age, ovarian reserve, race, BMI, presence of other potential causes of female infertility, or presence of male factor infertility?
5. KQ 5: What are the comparative safety and effectiveness of available treatment strategies for couples with male factor infertility and no evidence of an underlying diagnosis associated with infertility in the female partner? o a. Does the optimal treatment strategy vary by characteristics in either partner such as age, ovarian reserve, race, or BMI?
6. KQ 6: What are the short- and long-term health outcomes of donors in infertility? a. For female oocyte donors: 1. Do specific aspects of the pre-donation evaluation identify potential donors at greater risk for short- or long-term adverse outcomes (e.g., OHSS, quality-of-life issues)? 2. Do short- and long-term outcomes differ among different stimulation/retrieval protocols? b. For male semen donors: 1. Are there long-term health, quality-of-life, or other adverse outcomes associated with donation?
7. Across All KQs.

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Advantages of Recombinant Follicle-Stimulating Hormone over Human Menopausal Gonadotropin in Intrauterine Insemination: A Randomized Clinical Trial in Polycystic Ovary Syndrome-Associated Infertility.2015
Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.2014
Role of luteal phase support on gonadotropin ovulation induction cycles in patients with polycystic ovary syndrome.2014
Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome.2011
Prospective, randomized study comparing highly purified urinary follicle-stimulating hormone (FSH) and recombinant FSH for in vitro fertilization/intracytoplasmic sperm injection in patients with polycystic ovary syndrome.2010
Laparoscopic ovarian diathermy after clomiphene failure in polycystic ovary syndrome: is it worthwhile? A randomized controlled trial.2011
Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial.2010
Intrauterine insemination versus timed intercourse with clomiphene citrate in polycystic ovary syndrome: a randomized controlled trial.2011
Low-dose hCG as trigger day and 35 hr later have different ovarian hyperstimulation syndrome occurrence in females undergoing In vitro fertilization: An RCT.2017
Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome.2009
Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome.
The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment.2014
Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.2007
Randomized Trial of a Lifestyle Program in Obese Infertile Women.2016
Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins.2011
Extending clomiphene treatment in clomiphene-resistant women with PCOS: a randomized controlled trial.2008
Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome.2016
Comparison of assisted reproductive technology outcomes in infertile women with polycystic ovary syndrome: In vitro maturation, GnRH agonist, and GnRH antagonist cycles.2012
Increased rates of complications in singleton pregnancies of women previously diagnosed with polycystic ovary syndrome predominantly in the hyperandrogenic phenotype.2017
Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.2017
Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial.2017
Exposure to human chorionic gonadotropin during in vitro maturation does not improve the maturation rate and developmental potential of immature oocytes from patients with polycystic ovary syndrome.2008
Letrozole as the first-line treatment of infertile women with poly cystic ovarian syndrome (PCOS) compared with clomiphene citrate: A clinical trial.2016
Clomiphene citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial.
Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.2017
Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.
Comparison of gonadotropin-releasing hormone agonists and antagonists in assisted reproduction cycles of polycystic ovarian syndrome patients.2010
Recombinant FSH Compared to Clomiphene Citrate as the First-Line in Ovulation Induction in Polycystic Ovary Syndrome Using Newly Designed Pens: A Randomized Controlled Trial.2016
Fertility treatment and childhood type 1 diabetes mellitus: a nationwide cohort study of 565,116 live births.2016
Preterm Delivery and Low Birth Weight Among Neonates Conceived With Intracytoplasmic Sperm Injection Compared With Conventional In Vitro Fertilization.2018
The long-term prognosis for live birth in couples initiating fertility treatments.2017
A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.
PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene.
Effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase compared with GnRH agonist long protocol in non-obese and obese patients with polycystic ovary syndrome undergoing IVF/ICSI.2012
Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study.2011
Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study.2008
Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome.2015
The laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome; a randomized controlled trial.2012
Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial.2012
Laparoscopic ovarian diathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycystic ovary syndrome: a randomized controlled trial.2010
Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial.2011
The impact of a gonadotropin-releasing hormone antagonist on gonadotropin ovulation induction cycles in women with polycystic ovary syndrome: a prospective randomized study.2011
Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients.2010
Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial.2016
Gonadotrophins versus clomifene citrate with or without intrauterine insemination in women with normogonadotropic anovulation and clomifene failure (M-OVIN): a randomised, two-by-two factorial trial.2018
Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.2017
Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome.
Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial.
Clomiphene citrate plus tamoxifen versus laparoscopic ovarian drilling in women with clomiphene-resistant polycystic ovary syndrome.2010
Effect of hCG priming on embryonic development of immature oocytes collected from unstimulated women with polycystic ovarian syndrome.
Comparison between two clomiphene citrate protocols for induction of ovulation in clomiphene resistant polycystic ovary syndrome.2014
Letrozole versus laparoscopic ovarian drilling in infertile women with PCOS resistant to clomiphene citrate.2017
Clomiphene citrate, metformin or a combination of both as the first line ovulation induction drug for Asian Indian women with polycystic ovarian syndrome: A randomized controlled trial.2015
Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial. 2018
Tamoxifen versus clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: A prospective randomized trial.2017
Clomiphene citrate plus cabergoline versus clomiphene citrate for induction of ovulation in infertile euprolactinemic patients with polycystic ovary syndrome: A randomized clinical trial.
Effects of fertility drugs on cancers other than breast and gynecologic malignancies.2015
Impact of preimplantation genetic screening on donor oocyte-recipient cycles in the United States.2017
Outcomes of in vitro fertilization with preimplantation genetic diagnosis: an analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011-2012.2016
Cryopreserved oocyte versus fresh oocyte assisted reproductive technology cycles, United States, 2013.2017
Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children.2015
Melanoma risk after ovarian stimulation for in vitro fertilization.2015
Assisted hatching and live births in first-cycle frozen embryo transfers.2017
Birth Outcomes by Infertility Treatment: Analyses of the Population-Based Cohort: Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART).-- Not Found --
The association between the number of oocytes retrieved for IVF, perinatal outcome and obstetric complications.
Elective single embryo transfer in women less than age 38 years reduces multiple birth rates, but not live birth rates, in United States fertility clinics.2016
The Groningen ART cohort study: the effects of ovarian hyperstimulation and the IVF laboratory procedures on neurological condition at 2 years.2011
Frozen-thawed embryo transfer in a natural or mildly hormonally stimulated cycle in women with regular ovulatory cycles: a RCT.2015
Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles.2016
Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols.2017
Abnormal implantation after fresh and frozen in vitro fertilization cycles.2017
Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation.2018
Assisted reproductive technology and birth defects among liveborn infants in Florida, Massachusetts, and Michigan, 2000-2010. 2016
Birthweight in infants conceived through in vitro fertilization following blastocyst or cleavage-stage embryo transfer: a national registry study. 2018
Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infants. 2018
Is the type of gonadotropin-releasing hormone suppression protocol for ovarian hyperstimulation associated with ectopic pregnancy in fresh autologous cycles for in vitro fertilization?
State Insurance Mandates and Multiple Birth Rates After In Vitro Fertilization.2016
US oocyte donors: a retrospective study of medical and psychosocial issues.2009
Ovulation triggering with GnRH agonist vs. hCG in the same egg donor population undergoing donor oocyte cycles with GnRH antagonist: a prospective randomized cross-over trial.
Complications related to ovarian stimulation and oocyte retrieval in 4052 oocyte donor cycles.2008
Triggering with human chorionic gonadotropin or a gonadotropin-releasing hormone agonist in gonadotropin-releasing hormone antagonist-treated oocyte donor cycles: findings of a large retrospective cohort study.2009
The incidence of both serious and minor complications in young women undergoing oocyte donation.2008
Post-laparoscopic oral contraceptive combined with Chinese herbal mixture in treatment of infertility and pain associated with minimal or mild endometriosis: a randomized controlled trial.
In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk.2013
Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis.2012
Practice patterns and outcomes with the use of single embryo transfer in the United States.2010
Dienogest treatment after ovarian endometrioma removal in infertile women prior to IVF.2017
Recombinant FSH increases live birth rates as compared to clomiphene citrate in intrauterine insemination cycles in couples with subfertility: a prospective randomized study.2015
Cancer risk among children born after assisted conception.2013
Single versus double intrauterine insemination in multi-follicular ovarian hyperstimulation cycles: a randomized trial.2010
Immobilization or mobilization after IUI: an RCT.2017
Intracytoplasmic morphologically selected sperm injection versus conventional intracytoplasmic sperm injection: a randomized controlled trial.
Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection.2015
Laser assisted zona hatching does not improve live birth rate in patients undergoing their first ICSI cycles.2013
Is intracytoplasmic morphologically selected sperm injection (IMSI) beneficial in the first ART cycle? a multicentric randomized controlled trial.2013
Clinical outcomes and development of children born after intracytoplasmic sperm injection (ICSI) using extracted testicular sperm or ejaculated extreme severe oligo-astheno-teratozoospermia sperm: a comparative study.
National study of factors influencing assisted reproductive technology outcomes with male factor infertility.2011
Clinical outcome of intracytoplasmic injection of spermatozoa morphologically selected under high magnification: a prospective randomized study.2011
Salivary testosterone concentrations in pubertal ICSI boys compared with spontaneously conceived boys.2011
Intracytoplasmic morphologically selected sperm injection and congenital birth defects: a retrospective cohort study.2016
Moderate aerobic exercise training for improving reproductive function in infertile patients: A randomized controlled trial.2017
Transfer of Fresh versus Frozen Embryos in Ovulatory Women.2018
Use of Intracytoplasmic Sperm Injection and Birth Outcomes in Women Conceiving through In Vitro Fertilization.2017
Assisted reproductive technology and perinatal outcomes: conventional versus discordant-sibling design.2016
The effect on clinical results of adding recombinant LH in late phase of ovarian stimulation of patients with repeated implantation failure: A pilot study. 2017
Diagnostic and remedial capability of transcervical falloposcopy in conjunction with laparoscopy.2014
Cost-effectiveness of tubal patency tests.2013
Hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy as a treatment for hydrosalpinges prior to IVF or ICSI: an RCT.2016
Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.2016
Transcutaneous Electrical Acupoint Stimulation Improves the Outcomes of In Vitro Fertilization: A Prospective, Randomized and Controlled Study.-- Not Found --
Time-limited hydrotubation combined with clomiphene citrate treatment for unexplained infertility.2015
Dehydroepiandrosterone decreases the age-related decline of the in vitro fertilization outcome in women younger than 40 years old.2015
Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011.2014
Effect of luteal phase support with vaginal progesterone in intrauterine insemination cycles with regard to follicular response: a prospective randomized study.-- Not Found --
A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).2014
Effect of Pertubation on Pregnancy Rates before Intrauterine Insemination Treatment in Patients with Unexplained Infertility.2014
IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.2014
A prospective randomized study to evaluate the effect of hyaluronic acid sperm selection on the intracytoplasmic sperm injection outcome of patients with unexplained infertility having normal semen parameters.2013
Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection.2013
Advantages of recombinant follicle-stimulating hormone over human menopausal gonadotropin for ovarian stimulation in intrauterine insemination: a randomized clinical trial in unexplained infertility.2013
Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials.2013
Clomiphene citrate versus high doses of gonadotropins for in vitro fertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial.2012
Long-term outcome in couples with unexplained subfertility and an intermediate prognosis initially randomized between expectant management and immediate treatment.2012
The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders.2011
Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study.2010
A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial.2010
Pregnancy outcome after ovulation induction with aromatase inhibitors or clomiphene citrate in unexplained infertility.2009
Randomized controlled pilot trial of luteal phase recombinant FSH stimulation in poor responders.2008
Prognosis of oocyte donation cycles: a prospective comparison of the in vitro fertilization-embryo transfer cycles of recipients who used shared oocytes versus those who used altruistic donors.2009
Impact of luteal phase support on pregnancy rates in intrauterine insemination cycles: a prospective randomized study.2009
Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial.2008
Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination.2008
Comparison of different gonadotrophin preparations in intrauterine insemination cycles for the treatment of unexplained infertility: a prospective, randomized study.2007
Effects of piroxicam administration on pregnancy outcome in intrauterine insemination (IUI) cycles: a randomized clinical trial.2016
Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial.2015
Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.2015
Antagonist protocol versus clomiphene in unexplained infertility: A randomized controlled study.2016
A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.2017
Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial.2018
Assisted Reproductive Technology and Newborn Size in Singletons Resulting from Fresh and Cryopreserved Embryos Transfer.2017
Intrauterine insemination with gonadotropin stimulation or in vitro fertilization for the treatment of unexplained subfertility: a randomized controlled trial.2017
Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A randomized trial.2017
Follicle stimulating hormone versus clomiphene citrate in intrauterine insemination for unexplained subfertility: a randomized controlled trial.2018
Cervical mucus removal prior to intrauterine insemination: a randomized trial.2018
Ovulation triggering with GnRH agonist vs. hCG in the same egg donor population undergoing donor oocyte cycles with GnRH antagonist: a prospective randomized cross-over trial.2009
Effectiveness of corifollitropin alfa used for ovarian stimulation of poor responder patients.2016
Effect of Melatonin on the Outcome of Assisted Reproductive Technique Cycles in Women with Diminished Ovarian Reserve: A Double-Blinded Randomized Clinical Trial.2017
Comparison of modified agonist, mild-stimulation and antagonist protocols for in vitro fertilization in patients with diminished ovarian reserve.2018
Prospective randomized study for hydrotubation with or without lidocaine before intrauterine insemination in unexplained infertility2012
The effect of luteal phase support on pregnancy rates of the stimulated intrauterine insemination cycles in couples with unexplained infertility.2010
Use of Letrozole versus clomiphene-estradiol for treating infertile women with unexplained infertility not responding well to clomiphene alone, comparative study.2018

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