Abstract
Introduction
About 17% of couples in industrialised countries seek help for infertility, which may be caused by ovulatory failure, tubal damage or endometriosis, or a low sperm count. In developed countries, 80% to 90% of couples attempting to conceive are successful after 1 year and 95% after 2 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for infertility caused by ovulation disorders? What are the effects of treatments for tubal infertility? What are the effects of treatments for infertility associated with endometriosis? What are the effects of treatments for unexplained infertility? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 55 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: clomifene; drug-induced ovarian suppression; gonadotrophin priming of oocytes before in vitro maturation; gonadotrophins; gonadotrophin-releasing hormone agonists plus gonadotrophins; gonadotrophin-releasing hormone antagonists; in vitro fertilisation; intrauterine insemination alone, or combined with gonadotrophins or clomifene; laparoscopic ablation of endometrial deposits; laparoscopic ovarian drilling; laparoscopic removal; metformin; ovarian wedge biopsy; pulsatile gonadotrophin-releasing hormone; selective salpingography plus tubal catheterisation; tamoxifen; tubal flushing; and tubal surgery before in vitro fertilisation.
Key Points
About 17% of couples in industrialised countries seek help for infertility, which may be caused by ovulatory failure, tubal damage or endometriosis, or a low sperm count.
In women with ovulatory disorders, clomifene and metformin increase ovulation and pregnancy rates. There is some evidence that tamoxifen may have similar efficacy to clomifene, but we found no RCTs of sufficient quality comparing tamoxifen with placebo, and it is rarely used nowadays.
Gonadotrophins may increase pregnancy rates but may increase ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy.
Laparoscopic ovarian drilling may be as effective as gonadotrophins.
We don't know whether pulsed gonadotrophin-releasing hormone (GnRH), or gonadotrophin priming of oocytes before in vitro maturation increase pregnancy rates.
Consensus suggests that in vitro fertilisation may lead to pregnancy, but increases the risks of multiple pregnancy unless single embryo replacement is practised.
We don't know whether GnRH agonists plus gonadotrophins increase pregnancy rates compared with gonadotrophins alone but the combination treatment may be associated with an increased risk of OHSS. We don't know how effective GnRH antagonists are because we found few trials.
We don't know whether intrauterine insemination alone, or combined with gonadotrophins or clomifene is effective for infertility caused by ovulation disorders.
In women with tubal infertility, tubal flushing may increase pregnancy rates, with oil soluble media possibly more effective than water soluble media; however, we found few trials solely in women with tubal infertility.
Tubal surgery before in vitro fertilisation may increase pregnancy rates compared with no treatment in women with hydrosalpinges, but we don't know whether selective salpingography plus tubal catheterisation is beneficial.
Consensus suggests that in vitro fertilisation is beneficial.
In women with endometriosis, adding gonadotrophins to intrauterine insemination increases live birth rates compared with no treatment and increases pregnancy rates compared with intrauterine insemination alone.
Laparoscopic ablation of endometrial deposits may increase live birth rates compared with diagnostic laparoscopy.
Drugs to induce ovarian suppression may not increase pregnancy rates.
Consensus suggests that in vitro fertilisation may be beneficial.
Tubal flushing with oil-based media may increase live birth rates and pregnancy rates in women with minimal or mild endometriosis.
In women with unexplained infertility, clomifene does not increase live birth rates. It is not better than expectant management.
Intrauterine insemination without ovarian stimulation does not result in a significant increase in live birth rates.
Intrauterine insemination plus controlled ovarian stimulation may increase pregnancy rates but may increase OHSS and multiple pregnancy.
In vitro fertilisation may be beneficial, however, evidence is insufficient to make any conclusions.
Clinical context
About this condition
Definition
This review focuses on infertility related to factors associated with the woman rather than the man. Normal fertility has been defined as achieving a pregnancy within 2 years by regular unprotected sexual intercourse. However, many define infertility as the failure to conceive after 1 year of unprotected intercourse. Infertility can be primary, in women who have never conceived, or secondary, in women who have previously conceived. This review will deal with infertility owing to endometriosis, ovulation disorders, tubal infertility, and unexplained infertility. Endometriosis is a progressive disease that occurs when the endometrial tissue lining the uterus grows outside the uterus and attaches to the ovaries, fallopian tubes, or other organs in the abdominal cavity (See endometriosis). Ovulation disorders are defined by the failure of an ovum to be expelled because of a malfunction in the ovary, and are a major cause of infertility. Tubal infertility is the inability to conceive owing to a blockage in one or both fallopian tubes, and is a common cause of infertility. Unexplained infertility is a term used to describe couples with infertility in whom standard investigations including semen analysis, tests of ovulation, and tubal patency have failed to detect any gross abnormality.
Incidence/ Prevalence
Although there is no evidence of a major change in the prevalence of female infertility, many more couples are seeking help than previously. Currently, about 1/6 (17%) couples in industrialised countries will seek medical advice for infertility. Rates of primary infertility vary widely between countries, ranging from <6% in China, Malawi, Tanzania, and Zambia; 9% in the Philippines; >10% in Finland, Sweden, and Canada; and 18% in Switzerland. Reported rates of secondary infertility are less reliable.
Aetiology/ Risk factors
In the UK, about 10% to 20% of infertility cases are unexplained. The rest are caused by ovulatory failure (27%), tubal damage (14%), endometriosis (5%), low sperm count or quality (19%), and other causes (5%).
Prognosis
In developed countries, 80% to 90% of couples attempting to conceive are successful after 1 year and 95% after 2 years. The chances of becoming pregnant vary with the cause and duration of infertility, the woman's age, the woman's previous pregnancy history, and the availability of different treatment options. For the first 2 to 3 years of unexplained infertility, cumulative conception rates remain high (27–46%) but decrease with increasing age of the woman and duration of infertility. The background rates of spontaneous pregnancy in infertile couples can be calculated from longitudinal studies of infertile couples who have been observed without treatment.
Aims of intervention
To achieve the delivery of one healthy baby; to reduce the distress associated with infertility, with minimal adverse effects.
Outcomes
Live births; adverse effects including miscarriages, multiple pregnancies, incidence of ovarian hyperstimulation syndrome; satisfaction with services and treatments, acceptance of childlessness if treatment is unsuccessful; pregnancy and ovulation rates are important intermediate outcomes. Spontaneous pregnancies can occur without treatment in couples who are considered infertile. Effectiveness of treatments for infertility should be assessed on the basis of pregnancy rates over and above the spontaneous pregnancy rates, otherwise the impacts of treatments may be overestimated.
Methods
Clinical Evidence search and appraisal October 2009. The following databases were used to identify studies for this systematic review: Medline 1966 to October 2009, Embase 1980 to October 2009, and The Cochrane Database of Systematic Reviews 2009, Issue 4 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blind, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as “open”, “open label”, or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (into high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com). Crossover design: For infertility, RCTs with a crossover design may overestimate the treatment effect because pregnancies occurring in the first half of the trial will remove couples from the second half. Crossover trials were included in some systematic reviews where no or few RCTs using a parallel group design were available. Ideally, only data from the first half of the trial, before crossover, should be used. However, post-crossover results are reported in the absence of pre-crossover results. However, a study that used a computer model to compare the results of crossover and parallel designed trials suggests that any overestimation may be clinically irrelevant.
Table 1.
GRADE evaluation of interventions for female infertility
| Important outcomes | Live birth rates, pregnancy rates, ovulation rates, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for infertility caused by ovulation disorders? | |||||||||
| 3 (133) | Pregnancy rate | Clomifene v placebo | 4 | –2 | 0 | 0 | +2 | High | Quality points deducted for sparse data and results post-crossover. Effect size points added for OR >5 |
| 3 (133) | Ovulation rate | Clomifene v placebo | 4 | –2 | 0 | 0 | +2 | High | Quality points deducted for sparse data and results post-crossover. Effects size point added for OR >5 |
| 1 (95) | Live birth rate | Clomifene v tamoxifen | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 3 (256) | Pregnancy rate | Clomifene v tamoxifen | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (95) | Ovulation rate | Clomifene v tamoxifen | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (72) | Live birth rate | Clomifene v laparoscopic ovarian drilling | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for additional treatments |
| 1 (72) | Pregnancy rate | Clomifene v laparoscopic ovarian drilling | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for additional treatments |
| 1 (72) | Ovulation rate | Clomifene v laparoscopic ovarian drilling | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 2 (50) | Live birth rate | Metformin v placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and low event rate leading to wide confidence intervals |
| 6 (479) | Pregnancy rate | Metformin v placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 13 (875) | Ovulation rate | Metformin v placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 3 (600) | Live birth rate | Metformin v clomifene | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for significant statistical heterogeneity in analysis |
| 3 (600) | Pregnancy rate | Metformin v clomifene | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for significant statistical heterogeneity in analysis. Consistency point deducted for conflicting results |
| 3 (594 women, 2470 cycles) | Ovulation rate | Metformin v clomifene | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for significant statistical heterogeneity in analysis. Consistency point deducted for conflicting results |
| 4 (752) | Live birth rate | Metformin plus clomifene v clomifene alone | 4 | 0 | 0 | 0 | 0 | High | |
| 8 (976) | Pregnancy rate | Metformin plus clomifene v clomifene alone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for significant statistical heterogeneity. Consistency point deducted for different results between analyses |
| 12 (2700) | Ovulation rate | Metformin plus clomifene v clomifene alone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for significant statistical heterogeneity. Consistency point deducted for different results between analyses |
| 7 (627) | Pregnancy rate | Urinary follicle-stimulating hormone v hMG | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for methodological weaknesses in included studies (blinding and method of randomisation not reported) |
| 7 (627) | Ovulation rate | Urinary follicle-stimulating hormone v hMG | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for methodological weaknesses in included studies (blinding and method of randomisation not reported) |
| 3 (122) | Live birth rate | Gonadotrophins plus metformin v gonadotrophins alone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| at least 4 (at least 154) | Pregnancy rate | Gonadotrophins plus metformin v gonadotrophins alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and inclusion of post-crossover results from one RCT |
| 2 (305) | Live birth rate | Urinary hCG plus clomifene citrate v clomifene citrate alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for methodological weakness in included RCTs (underpowered and no blinding) |
| 2 (305) | Pregnancy rate | Urinary hCG plus clomifene citrate v clomifene citrate alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for methodological weakness in one RCT (underpowered and no blinding) |
| 2 (305) | Ovulation rate | Urinary hCG plus clomifene citrate v clomifene citrate alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for methodological weakness in one RCT (underpowered and no blinding) |
| 3 (211) | Pregnancy rate | Gonadotrophin-releasing hormone agonists plus gonadotrophins v gonadotrophins alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for methodological weaknesses in included RCTs (not stating method of randomisation and lack of blinding) |
| 3 (187) | Ovulation rate | Gonadotrophin-releasing hormone agonists plus gonadotrophins v gonadotrophins alone | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data and methodological weaknesses in included RCTs (not stating method of randomisation and lack of blinding) |
| 2 (204) | Live birth rate | Gonadotrophin-releasing hormone antagonists v gonadotrophin-releasing hormone agonists in an IVF cycle | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting |
| 4 (305) | Pregnancy rate | Gonadotrophin-releasing hormone antagonists v gonadotrophin-releasing hormone agonists in an IVF cycle | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for inclusion of unpublished data and methodological flaws in 2 RCTs (not stating method of randomisation) |
| 1 (28) | Pregnancy rate | Pulsatile gonadotrophin-releasing hormone v clomifene | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and methodological weaknesses |
| 1 (28) | Ovulation rate | Pulsatile gonadotrophin-releasing hormone v clomifene | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and methodological weaknesses |
| 2 (218) | Live birth rate | Laparoscopic ovarian drilling v gonadotrophins | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for inclusion of additional treatments in one RCT. |
| at least 3 (at least 254) | Pregnancy rate | Laparoscopic ovarian drilling v gonadotrophins | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for inclusion of additional treatments |
| 1 (50) | Ovulation rate | Laparoscopic ovarian drilling v gonadotrophins | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (109) | Live birth rate | Laparoscopic ovarian drilling v metformin | 4 | –1 | 0 | 0 | 0 | Moderate | Quality points deducted for sparse data |
| 2 (270) | Pregnancy rate | Laparoscopic ovarian drilling v metformin | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting. Directness point deducted for inclusion of other treatments in one RCT |
| 1 (161) | Ovulation rate | Laparoscopic ovarian drilling v metformin | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting and sparse data. Directness point deducted for inclusion of other treatments in one RCT |
| 1 (42) | Live birth rate | Laparoscopic ovarian drilling v laparoscopic ovarian drilling plus metformin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and methodological weaknesses |
| 1 (42) | Pregnancy rate | Laparoscopic ovarian drilling v laparoscopic ovarian drilling plus metformin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and methodological weaknesses |
| 3 (272) | Live birth rate | Metformin plus IVF v IVF alone | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for inclusion of ICSI in some studies |
| 5 (426) | Pregnancy rate | Metformin plus IVF v IVF alone | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for inclusion of ICSI in some studies and different result in subgroup analysis |
| 3 (105) | Pregnancy rates | Priming with gonadotrophins v no priming | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for conflicting results |
| What are the effects of treatments for tubal infertility? | |||||||||
| 1 (31) | Pregnancy rate | Tubal flushing with oil-based media v water-based | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis |
| 3 (295) | Live birth rate | Tubal surgery v no treatment/medical treatment | 4 | 0 | 0 | –2 | +1 | Moderate | Directness points deducted for narrow inclusion criteria and use of different comparators. Effect size point added for RR >2 |
| 3 (295) | Pregnancy rate | Tubal surgery v no treatment/medical treatment | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for narrow inclusion criteria and use of different comparators |
| 1 (63) | Pregnancy rate | CO2 laser adhesiolysis v diathermy adhesiolysis | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of treatments for infertility associated with endometriosis? | |||||||||
| 11 (557) | Pregnancy rate | Ovulation suppression v placebo | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for wide range of interventions |
| 1 (103) | Live birth rate | Intrauterine insemination plus gonadotrophins v no treatment | 4 | –1 | 0 | –1 | +2 | High | Quality point deducted for sparse data. Directness point deducted for narrow inclusion criteria. Effect size points added for OR >5 |
| 1 (57) | Pregnancy rate | Intrauterine insemination plus gonadotrophins v intrauterine insemination alone | 4 | –1 | 0 | 0 | +2 | High | Quality point deducted for sparse data. Effect size points added for OR >5 |
| 1 (51) | Pregnancy rate | Intrauterine insemination plus clomifene v no treatment/expectant management | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for no pre-crossover statistical assessment between groups |
| 1 (62) | Live birth rate | Tubal flushing with oil soluble contrast media v no treatment/expectant management | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis |
| 1 (62) | Pregnancy rate | Tubal flushing with oil soluble contrast media v no treatment/expectant management | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis |
| 2 (437) | Pregnancy rate | Laparoscopic surgery v no surgery | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for composite outcome |
| What are the effects of treatments for unexplained fertility? | |||||||||
| 1 (387) | Live birth rate | Clomifene v placebo/expectant management | 4 | 0 | 0 | 0 | 0 | High | |
| 2 (460) | Pregnancy rate | Clomifene v placebo/expectant management | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for inclusion of one study published in abstract form |
| 1 (384) | Live birth rate | Unstimulated IUI v expectant management | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (384) | Pregnancy rate | Unstimulated IUI v expectant management | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (113) | Live birth rate | Unstimulated IUI v IVF | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (51) | Pregnancy rate | Stimulated IUI v expectant management | 4 | –2 | 0 | –1 | +1 | Low | Quality points deducted for sparse data and poor follow-up. Directness point deducted for inclusion of women with endometriosis. Effect size point added for effect size >2 |
| 1 (40) | Pregnancy rate | Stimulated IUI v clomifene | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis |
| 4 (396) | Live birth rate | Stimulated IUI v unstimulated IUI | 4 | 0 | 0 | 0 | +1 | High | Effect size point added for effect size >2 |
| 4 (396) | Pregnancy rate | Stimulated IUI v unstimulated IUI | 4 | 0 | 0 | 0 | +1 | High | Effect size point added for effect size >2 |
| 1 (118) | Live birth rate | Stimulated IUI v IVF | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (51) | Live birth rate | IVF v expectant management | 4 | –2 | 0 | –1 | +2 | Moderate | Quality points deducted for sparse data and unequal follow-up between groups. Directness point deducted for uncertainty about significance of result. Effect size points added for effect size >5 |
| 2 (86) | Pregnancy rate | IVF v expectant management | 4 | –2 | 0 | 0 | +1 | Moderate | Quality points deducted for sparse data and unequal follow-up between groups. Effect size point added for effect size >2 |
Type of evidence: 4 = RCT. Consistency: similarity of results across studies. Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.hCG, human chorionic gonadotrophin; hMG, human menopausal gonadotrophin; ICSI, intracytoplasmic sperm injection; IUI, intrauterine insemination; IVF, in vitro fertilisation.
Glossary
- Anovulation
is the failure to ovulate (expel a mature oocyte) owing to dysfunction of the ovary or suppression by drug treatment. Anovulation is a common cause of female infertility. Most often, women who do not ovulate also do not menstruate (amenorrhoea).
- Assisted hatching procedure
Assisted hatching is a process to breach the zona pellucida of an embryo, by either laser or chemical processes, potentially to improve its implantation potential.
- Delayed in vitro fertilisation
In vitro fertilisation treatment after 6 months of being assessed in an infertility clinic after at least 12 months of infertility.
- Endometriosis
is a progressive disease that occurs when the endometrial tissue lining the uterus grows outside the uterus and attaches to the ovaries, fallopian tubes, or other organs in the abdominal cavity. Symptoms include painful menstrual periods, abnormal menstrual bleeding, and pain during or after sexual intercourse.
- Gonadotrophin priming of oocytes
This is the in vitro maturation of oocytes using gonadotrophins (hormones stimulate and control reproductive activity) from the germinal vesicle (early) stage of development to the metaphase II (mature) stage.
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Hydrosalpinges
is the abnormal distension of one or both fallopian tubes owing to fluid build up, usually because of inflammation.
- Hydrotubation
Flushing of the fallopian tubes through the cervix and uterine cavity to remove surgical debris and reduce the incidence of tubal reocclusion.
- Immediate in vitro fertilisation
In vitro fertilisation treatment within 6 months of being assessed in an infertility clinic after at least 12 months of infertility.
- In vitro fertilisation
(IVF) is a technique where female oocytes (eggs) are fertilised with sperm from a male partner outside the body in a fluid medium in the laboratory. Embryos are transferred later to the uterus using a special catheter.
- Long agonist protocol
is the most widely used protocol for an in vitro fertilisation (IVF) cycle, which involves starting the gonadotrophin-releasing hormone (GnRH) agonist usually on the 21st day of the menstrual cycle. Ovarian stimulation with follicle-stimulating hormone (FSH) then starts a couple of days after the onset of menstruation.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Macrosurgery
Surgery without dedicated optical magnification.
- Microsurgery
Surgery involving optical magnification to allow the use of much finer instruments and suture material in addition to a non-touch technique, with the aim of minimising tissue handling and damage.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Ovarian hyperstimulation syndrome (OHSS)
can occur in mild, moderate, and severe forms. Mild ovarian hyperstimulation syndrome is characterised by fluid accumulation, as shown by weight gain, abdominal distension, and discomfort. Moderate ovarian hyperstimulation syndrome is associated with nausea and vomiting, ovarian enlargement, abdominal distension, discomfort, and dyspnoea. Severe ovarian hyperstimulation syndrome is a life-threatening condition, in which there is contraction of the intravascular volume, tense ascites, pleural and pericardial effusions, severe haemoconcentration, and the development of hepatorenal failure. Deaths have occurred, caused usually by cerebrovascular thrombosis, renal failure, or cardiac tamponade.
- Ovulation disorders
are defined by the failure of an ovum to be expelled owing to a malfunction in the ovary. Ovulation disorders are a major cause of infertility and can often be corrected with medication. Ovulation disorders often result in infrequent menstruation (oligomenorrhoea).
- Pituitary downregulation (long protocol)
This is the process by which the release of gonadotrophins from the pituitary gland is stopped after repeated administration of gonadotrophin-releasing hormone (GnRH) analogues; this in turn controls reproductive function.
- Polycystic ovary syndrome (PCOS)
results from an accumulation of incompletely developed follicles in the ovaries owing to chronic anovulation. PCOS is characterised by irregular or absent menstrual cycles, multiple small cysts on the ovaries (polycystic ovaries), mild hirsutism, and infertility. Many women also have increased insulin resistance.
- Pulsatile gonadotrophin-releasing hormone
is a hormone produced and released by the hypothalamus at intervals (pulses). Pulsatile gonadotrophin-releasing hormone controls the production and release of gonadotrophins from the pituitary gland, which in turn controls reproductive function.
- Salpingography
is a technique used to diagnose blockages in the fallopian tubes. It involves the radiographic imaging of the fallopian tubes after the injection of radio-opaque contrast medium (dye) through the cervix to the uterine cavity. If the fallopian tubes are open the dye flows into the tubes and then spills out to the abdominal cavity. This is documented in a series of x-ray images during the procedure. If tubes are blocked from the proximal end, a very narrow catheter is introduced under radiographic imaging (selective salpingography and tubal catheterisation) to remove the obstruction if possible.
- Second look laparoscopy
Laparoscopy performed some time after tubal surgery (either open or laparoscopic) with the aim of dividing adhesions relating to the initial procedure.
- Tubal flushing
involves injecting an oil or water soluble contrast medium into the fallopian tubes to flush out any blockages in the tubes. Flushing out any tubal “plugs” that may be causing proximal tubal occlusion using oil or water soluble media may have a fertility enhancing effect.
- Tubal infertility
is the inability to conceive owing to a blockage in one or both fallopian tubes and is a common cause of infertility. The tubal blockages are usually caused either by pelvic infection, such as pelvic inflammatory disease (PID) or endometriosis. Blockages may also be caused by scar tissue that forms after pelvic surgery.
- Tubal surgery
techniques are used to restore the patency of the fallopian tubes in women with tubal infertility as an alternative to in vitro fertilisation. Surgery may either be open microsurgery or laparoscopic microsurgery.
- Very low-quality evidence
Any estimate of effect is very uncertain.
See erectile dysfunction
See fibroids
See pelvic inflammatory disease
See varicocoele
See endometriosis
See polycystic ovary syndrome
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Siladitya Bhattacharya, Obstetrics & Gynaecology, Aberdeen Maternity Hospital, Aberdeen, UK.
Neil Johnson, University of Auckland, Auckland, New Zealand.
Hammed Akanji Tijani, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
Roger Hart, School of Women's and Infants Health, University of Western Australia and Fertility Specialists of Western Australia, Perth, Australia.
Shilpi Pandey, Assisted Reproduction Unit, University of Aberdeen, Aberdeen, UK.
Ahmed Fathy Gibreel, Obstetrics & Gynaecology Department, Mansoura University, Mansoura, Egypt.
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